The DOI matches its Crossref record; 75 of the 77 references it cites were found in a registry or an index; none of the 109 sources its claims cite is checked for support yet.
The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism
Open accessAbstract
Idiopathic hypogonadotropic hypogonadism (IHH) has an incidence of 1–10 cases per 100,000 births. About 60% of patients with IHH present with associated anosmia, also known as Kallmann syndrome, characterized by total or partial loss of olfaction. Many of the gene mutations associated with Kallmann syndrome have been mapped to KAL1 or FGFR1. However, together, these mutations account for only about 15% of Kallmann syndrome cases. More recently, mutations in PROK2 and PROKR2 have been linked to the syndrome and may account for an additional 5–10% of cases. The remaining 40% of patients with IHH have a normal sense of smell. Prior to 2003, the only gene linked to normosmic IHH was the gonadotropin-releasing hormone receptor gene. However, mutations in this receptor are believed to account for only 10% of cases. Subsequently, mutations in KISS1R, TAC3 and TACR3 were identified as causes of normosmic IHH. Certain genes, including PROK2 and FGFR1, are associated with both anosmic and normosmic IHH. Despite recent advances in the field, the genetic causes of the majority of cases of IHH remain unknown. This Review discusses genes associated with hypogonadotropic disorders and the molecular mechanisms by which mutations in these genes may result in IHH.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review summarizes the genetic and molecular basis of idiopathic hypogonadotropic hypogonadism (IHH), including Kallmann syndrome and normosmic IHH, organized by effects on GnRH neuron migration, secretion, and action. Despite identifying multiple causal genes, it concludes that the genetic basis of the vast majority of IHH cases remains unknown.
Key findings
- IHH has an incidence of 1–10 cases per 100,000 births; about 60% of patients have anosmia (Kallmann syndrome). KAL1 and FGFR1 mutations together account for only about 15% of Kallmann syndrome cases, while PROK2/PROKR2 mutations may account for an additional 5–10%.
- In normosmic IHH, GNRHR mutations account for 3.5–16% of sporadic cases and up to 40% of familial cases; KISS1R mutations represent about 5%, LEP/LEPR mutations less than 5%, and CHD7 mutations are predicted to account for 6% of all IHH cases. TAC3 or TACR3 mutations segregated with IHH in four of nine unrelated consanguineous families.
- Some genes, including PROK2 and FGFR1, are associated with both anosmic and normosmic IHH. Many cases are predicted to be polygenic, and sex-associated factors contribute to the phenotype, reinforced by a 5:1 male predominance.
- Reversal of hypogonadism after hormone treatment has been reported with KAL1, FGFR1, and GNRHR mutations, suggesting that partial loss of function may be compensated in some cases.
Methods
- Narrative review based on literature searches of Google Scholar and MEDLINE from 1990 to 2009 using keywords including “IHH,” “hypogonadism,” “Kallmann syndrome,” “anosmia,” “FGFR1,” “KAL1,” “GnRH,” “GPR54,” “kisspeptin,” “PROK2,” “PROKR2,” “leptin,” and “prohormone convertase.”
- No primary sample or new experimental data; the paper synthesizes human genetic findings with animal and in vitro functional studies, categorizing genes by roles in GnRH neuronal development/migration, GnRH secretion, or GnRH action.
Limitations
- The paper states that the genetic causes of the vast majority of IHH cases remain unknown and that the individual and/or combined roles of many recently identified genes are not yet completely understood.
- Evident from the text: this is a narrative review without a systematic quantitative synthesis; prevalence estimates are drawn from cited studies and vary widely (for example, GNRHR mutations in 3.5–16% of sporadic versus up to 40% of familial normosmic IHH), and several mechanisms are inferred from animal or in vitro models.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
76 Not checked yet · 20 Own interpretation · 18 No basis given · 1 Own result
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Accordingly, gene mutations associated with Kallmann syndrome encode proteins that regulate GnRH and olfactory neuronal migration.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Impaired migration of GnRH and olfactory neurons is the underlying cause of Kallmann syndrome.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite recent advances in the field, the genetic causes of the majority of cases of IHH remain unknown.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“More recently, mutations in PROK2 and PROKR2 have been linked to the syndrome and may account for an additional 5–10% of cases.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Other associated neurological and somatic abnormalities, such as synkinesia, cerebellar ataxia, sensorineural deafness, mental retardation, unilateral renal agenesis and cleft palate, may segregate with the Kallmann syndrome phenotype, which suggests a common genetic origin of these abnormalities.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Introduction
What the sources say
- Not checked yetcites [3] Cariboni, A. & Maggi, R. Kallmann's syndrome, a neuronal migration defect. Cell. Mol. Life Sci. 63, 2512–2526 (2006). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Evidence for the contribution of sex-associated factors in IHH is reinforced by the 5:1 male predominance of the disorder.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In some cases, the severity of hypogonadism and the presence of associated phenotypes in a pedigree present in a dimorphic distribution with incomplete penetrance.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Introduction
What the sources say
- Not checked yetcites [4] Pitteloud, N. et al. Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc. Natl Acad. Sci. USA 103, 6281–6286 (2006). source
- Not checked yetcites [5] Pitteloud, N. et al. Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes. Mol. Cell Endocrinol. 254–255, 60–69 (2006). source
- Not checked yetcites [6] Pitteloud, N. et al. Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism. J. Clin. Invest. 117, 457–463 (2007). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In addition, male patients often present with a more severe phenotype than affected female individuals within a given family.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, together, these mutations account for only about 15% of Kallmann syndrome cases.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Mutations in the tyrosine kinase domain of FGFR-1 are predicted to decrease or inhibit kinase activity by disrupting receptor conformation (Ile538Val, Asn724Lys, and Gly703Arg) and/or altering the normal pattern of phosphorylation of the kinase domain (Ala520Thr, Gly703Ser, Pro722Ser, Pro745Ser, and Pro772Ser).”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > FGFR1
What the sources say
- Not checked yetcites [5] Pitteloud, N. et al. Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes. Mol. Cell Endocrinol. 254–255, 60–69 (2006). source
- Not checked yetcites [13] Kim, S. H., Hu, Y., Cadman, S. & Bouloux, P. Diversity in fibroblast growth factor receptor 1 regulation: learning from the investigation of Kallmann syndrome. J. Neuroendocrinol. 20, 141–163 (2008). source
- Not checked yetcites [17] Böttcher, R. T. & Niehrs, C. Fibroblast growth factor signaling during early vertebrate development. Endocr. Rev. 26, 63–77 (2005). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Unlike the situation with KAL1 mutations, mutations in FGFR1 have been reported in patients with IHH without anosmia, termed normosmic IHH.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > FGFR1
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 38
- Probably not a substantial claim. 1
In the paper
“KAL1 is located on the X chromosome and encodes an extracellular cell adhesion protein, anosmin 1, essential for axonal guidance and migration of olfactory and GnRH neurons from the nasal placode to their final location in the brain.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > KAL1
What the sources say
- Not checked yetcites [7] Legouis, R. et al. The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules. Cell 67, 423–435 (1991). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The genetic mechanisms that underlie IHH in patients with a normal sense of smell are diverse and may involve genes that regulate development and/or GnRH secretion or action.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Anosmin 1 co-localizes with basic fibroblast growth factor receptor 1 (FGFR-1, discussed further below), in the olfactory bulb during development, which suggests that this protein is a component of FGFR-1 signaling.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > KAL1
What the sources say
- Not checked yetcites [8] Ayari, B. & Soussi-Yanicostas, N. FGFR1 and anosmin-1 underlying genetically distinct forms of Kallmann syndrome are co-expressed and interact in olfactory bulbs. Dev. Genes Evol. 217, 169–175 (2007). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This pattern suggests that changes may occur in more than one gene and/or that sex-associated modifying factors may contribute to the phenotype.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Introduction
What the sources say
- Not checked yetcites [4] Pitteloud, N. et al. Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc. Natl Acad. Sci. USA 103, 6281–6286 (2006). source
- Not checked yetcites [5] Pitteloud, N. et al. Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes. Mol. Cell Endocrinol. 254–255, 60–69 (2006). source
- Not checked yetcites [6] Pitteloud, N. et al. Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism. J. Clin. Invest. 117, 457–463 (2007). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mutations in KAL1 disrupt the migration of olfactory and GnRH neurons and are reported to be present in approximately 5–10% of patients with Kallmann syndrome (Table 1),7,9–11 with the highest prevalence seen in families with X-linked inheritance patterns.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > KAL1
What the sources say
- Not checked yetcites [7] Legouis, R. et al. The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules. Cell 67, 423–435 (1991). source
- Not checked yetcites [9] Franco, B. et al. A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature 353, 529–536 (1991). source
- Not checked yetcites [10] Hardelin, J. P. et al. Heterogeneity in the mutations responsible for X chromosome-linked Kallmann syndrome. Hum. Mol. Genet. 2, 373–377 (1993). source
- Not checked yetcites [11] Albuisson, J. et al. Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2). Hum. Mutat. 25, 98–99 (2005). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Two mutations (Asn267Lys and Glu514Lys) are expected to enhance heparin binding, which compromises the flexibility of anosmin 1.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > KAL1
What the sources say
- Not checked yetcites [13] Kim, S. H., Hu, Y., Cadman, S. & Bouloux, P. Diversity in fibroblast growth factor receptor 1 regulation: learning from the investigation of Kallmann syndrome. J. Neuroendocrinol. 20, 141–163 (2008). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In vitro studies indicate that a serine substitution at this position destabilizes the receptor, which results in misfolding and retention of the protein in the endoplasmic reticulum.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > FGFR1
What the sources say
- Not checked yetcites [4] Pitteloud, N. et al. Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc. Natl Acad. Sci. USA 103, 6281–6286 (2006). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The Cys163Tyr and Cys172Arg mutations are expected to prevent disulfide bond formation, which disrupts the tertiary structure of anosmin 1 and might result in misfolding and/or destabilization of the protein.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > KAL1
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In vitro studies have shown that substitution of Leu173, Trp178, and Pro290 in PROKR2 impairs the cell surface targeting of the receptor, probably because the receptor protein is incorrectly folded.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > PROK2 and PROKR2
What the sources say
- Not checked yetcites [29] Cole, L. W. et al. Mutations in prokineticin 2 and prokineticin receptor 2 genes in human gonadotrophin-releasing hormone deficiency: molecular genetics and clinical spectrum. J. Clin. Endocrinol. Metab. 93, 3551–3559 (2008). source
- Not checked yetcites [32] Monnier, C. et al. PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling activity. Hum. Mol. Genet. 18, 75–81 (2009). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Kiss1r−/− mice have underdeveloped gonads, low gonadotropins and steroid hormone levels, and incomplete gametogenesis.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > KISS1 and KISS1R
What the sources say
- Not checked yetcites [35] Seminara, S. B. et al. The GPR54 gene as a regulator of puberty. N. Engl. J. Med. 349, 1614–1627 (2003). source
- Not checked yetcites [47] Funes, S. et al. The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem. Biophys. Res. Commun. 312, 1357–1363 (2003). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A single amino acid substitution in PK2 (Arg73Cys) that greatly reduces activation of PK-R2-mediated stimulation of calcium signaling is predicted to disrupt a disulfide bond.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > PROK2 and PROKR2
What the sources say
- Not checked yetcites [28] Leroy, C. et al. Biallelic mutations in the prokineticin-2 gene in two sporadic cases of Kallmann syndrome. Eur. J. Hum. Genet. 16, 865–868 (2008). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Likewise, Prok2−/− mice fail to enter puberty, have low gonadotropin levels, and have a significant decrease in hypothalamic GnRH neurons.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > PROK2 and PROKR2
What the sources say
- Not checked yetcites [25] Matsumoto, S. et al. Abnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2. Proc. Natl Acad. Sci. USA 103, 4140–4145 (2006). source
- Not checked yetcites [26] Pitteloud, N. et al. Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc. Natl Acad. Sci. USA 104, 17447–17452 (2007). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, GnRH neurons in Prok2−/− mice were able to cross the cribriform plate (a horizontal plate of the ethmoid bone) to enter the central nervous system during embryonic development, but the neurons did not migrate into and populate the hypothalamus.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > PROK2 and PROKR2
What the sources say
- Not checked yetcites [24] Prosser, H. M., Bradley, A. & Caldwell, M. A. Olfactory bulb hypoplasia in Prokr2 null mice stems from defective neuronal progenitor migration and differentiation. Eur. J. Neurosci. 26, 3339–3344 (2007). source
- Not checked yetcites [26] Pitteloud, N. et al. Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc. Natl Acad. Sci. USA 104, 17447–17452 (2007). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Frameshift mutations that inactivate PK2 have been reported in sporadic cases of Kallmann syndrome28 and in families with a history of Kallmann syndrome or normosmic IHH.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > PROK2 and PROKR2
What the sources say
- Not checked yetcites [26] Pitteloud, N. et al. Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc. Natl Acad. Sci. USA 104, 17447–17452 (2007). source
- Not checked yetcites [28] Leroy, C. et al. Biallelic mutations in the prokineticin-2 gene in two sporadic cases of Kallmann syndrome. Eur. J. Hum. Genet. 16, 865–868 (2008). source
- Not checked yetcites [30] Abreu, A. P. et al. Loss-of-function mutations in the genes encoding prokineticin-2 or prokineticin receptor-2 cause autosomal recessive Kallmann syndrome. J. Clin. Endocrinol. Metab. 93, 4113–4118 (2008). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Another single amino acid substitution of the KiSS-1 receptor (Leu102Pro) identified in patients with IHH is located in the first extracellular loop of the receptor. The mutation decreases the expression of the receptor and impairs its signaling ability.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > KISS1 and KISS1R
What the sources say
- Not checked yetcites [51] Tenenbaum-Rakover, Y. et al. Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54 . J. Clin. Endocrinol. Metab. 92, 1137–1144 (2007). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In a study of 192 patients with Kallmann syndrome, 10 mutations in PROKR2 were identified,27 five (50%) of which resulted in single amino acid substitutions in the transmembrane domains (Leu173Arg, Trp178Ser, Pro290Ser, Met323Ile, and Val331Met).”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > PROK2 and PROKR2
What the sources say
- Not checked yetcites [27] Dodé, C. et al. Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet. 2, e175 (2006). source
plainn = 192- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similar to patients with PROKR2 mutations, Prokr2−/− mice exhibit olfactory bulb hypoplasia, hypogonadotropic hypogonadism, and a lack of GnRH neurons in the hypothalamus.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > PROK2 and PROKR2
What the sources say
- Not checked yetcites [25] Matsumoto, S. et al. Abnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2. Proc. Natl Acad. Sci. USA 103, 4140–4145 (2006). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, in mice, the IHH phenotype has been reported only in those homozygous for the Prok2 deletion, which suggests that one normal allele may compensate for the inactivity of the other.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > PROK2 and PROKR2
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The Gly93Asn mutation was found in all affected members of one family, whereas the Pro353Ser mutation was found in all affected members of two other families.63”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > TAC3 and TACR3
What the sources say
- Not checked yetcites [63] Topaloglu, A. K. et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for neurokinin B in the central control of reproduction. Nat. Genet. 41, 354–358 (2009). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These inactivating mutations account for less than 5% of normosmic IHH and have an autosomal recessive pattern of transmission (Table 1).”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > LEP and LEPR
What the sources say
- Not checked yetcites Table 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Leptin, encoded by LEP, is a fat-derived hormone that regulates food intake, energy expenditure and reproduction at the hypothalamic level.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > LEP and LEPR
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Glu250X is predicted to truncate the protein within its catalytic domain, whereas the mutation in the other allele (Ala213del) eliminates a highly conserved alanine near His208, a residue known to be critical for catalytic activity.67”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > PCSK1
What the sources say
- Not checked yetcites [67] Farooqi, S. & O'Rahilly, S. Genetics of obesity in humans. Endocr. Rev. 27, 710–718 (2006). source
boostedSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Inheritance is autosomal recessive and most patients have compound heterozygous GNRHR mutations.70”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > GnRH action: GNRHR
What the sources say
- Not checked yetcites [70] de Roux, N. GnRH receptor and GPR54 inactivation in isolated gonadotropic deficiency. Best Pract. Res. Clin. Endocrinol. Metab. 20, 515–528 (2006). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Accordingly, mice homozygous for an Asn222Asp NEC 1 substitution, which is also within the catalytic domain of the enzyme, are obese and have decreased fertility.69”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > PCSK1
What the sources say
- Not checked yetcites [69] Lloyd, D. J., Bohan, S. & Gekakis, N. Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice. Hum. Mol. Genet. 15, 1884–1893 (2006). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The second mutation causes a frameshift and the introduction of a premature stop codon in the catalytic domain of the enzyme.66”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > PCSK1
What the sources say
- Not checked yetcites [66] Jackson, R. S. et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat. Genet. 16, 303–306 (1997). source
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Large-scale screening indicates that GNRHR mutations account for 3.5–16% of sporadic cases of normosmic IHH and up to 40% of familial cases of normosmic IHH (Table 1).72”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > GnRH action: GNRHR
What the sources say
- Not checked yetcites [72] Bédécarrats, G. Y. & Kaiser, U. B. Mutations in the human gonadotropin-releasing hormone receptor: insights into receptor biology and function. Semin. Reprod. Med. 25, 368–378 (2007). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Activation of the GnRH receptor increases calcium mobilization and stimulates influx of extracellular calcium.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > GnRH action: GNRHR
What the sources say
- Not checked yetcites [70] de Roux, N. GnRH receptor and GPR54 inactivation in isolated gonadotropic deficiency. Best Pract. Res. Clin. Endocrinol. Metab. 20, 515–528 (2006). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Although the mutation in the other allele—Arg297Leu—only slightly decreased the activity of the KiSS-1 receptor, the combination of the two mutated alleles was enough to cause hypogonadism.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > KISS1 and KISS1R
What the sources say
- Not checked yetcites [52] Semple, R. K. et al. Two novel missense mutations in G protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 90, 1849–1855 (2005). source
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although no reports have been published on the molecular mechanisms by which mutations in PCSK1 cause hypogonadism, the impairment of GnRH prohormone precursor processing is probably involved in these cases.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > PCSK1
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This mutation is also within the catalytic domain and severely impairs the catalytic activity of the enzyme.68”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > PCSK1
What the sources say
- Not checked yetcites [68] Farooqi, I. S. et al. Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J. Clin. Endocrinol. Metab. 92, 3369–3373 (2007). source
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Only two of 11 mutations identified in transmembrane domains encode a partially functional receptor; the other nine encode completely inactive receptors.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > GnRH action: GNRHR
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The first report of a patient with congenital NEC 1 deficiency associated with obesity and hypogonadotropic hypogonadism was published in 1995.65”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > PCSK1
What the sources say
- Not checked yetcites [65] O'Rahilly, S. et al. Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N. Engl. J. Med. 333, 1386–1390 (1995). source
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“NKB is expressed in the arcuate nucleus and its receptor is expressed in GnRH neurons of rodents, which suggests it has a possible role in the regulation of GnRH secretion.63”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > TAC3 and TACR3
What the sources say
- Not checked yetcites [63] Topaloglu, A. K. et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for neurokinin B in the central control of reproduction. Nat. Genet. 41, 354–358 (2009). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Gln106Arg maps to the first extracellular loop of the GnRHR and decreases GnRH binding.71”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > GnRH action: GNRHR
What the sources say
- Not checked yetcites [71] de Roux, N. et al. A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. N. Engl. J. Med. 337, 1597–1602 (1997). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Molecular mechanisms that underlie IHH in patients with a normal sense of smell are diverse and may involve genes that regulate development and/or GnRH secretion or action”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Conclusions > Key points
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While some genetic mutations are sufficient to cause IHH, other cases are predicted to result from the combination of more than one genetic abnormality.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Conclusions
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The parents of the affected siblings were phenotypically normal, despite each being heterozygous for one of these substitutions.73”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > GnRH action: GNRHR
What the sources say
- Not checked yetcites [73] Beranova, M. et al. Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 86, 1580–1588 (2001).
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The Arg262Gln substitution is located in the third intracellular loop, the main site of G-protein interaction.”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > GnRH action: GNRHR
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IHH with anosmia (Kallmann syndrome) is caused by the defective developmental migration of gonadotropin-releasing hormone (GnRH) and olfactory neurons; associated genes encode proteins involved in this migration”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Conclusions > Key points
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper relies on this without support.
The major underlying cause of IHH is failure to activate pulsatile secretion of gonadotropin-releasing hormone (GnRH) during puberty.
“The major underlying cause of IHH is failure to activate pulsatile secretion of gonadotropin-releasing hormone (GnRH) during puberty, a developmental stage characterized by a substantial increase in the frequency and amplitude of pulses of this hormone.”
The paper relies on this without support.
Impaired migration of GnRH and olfactory neurons is the underlying cause of Kallmann syndrome.
“Impaired migration of GnRH and olfactory neurons is the underlying cause of Kallmann syndrome (IHH associated with anosmia).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“By contrast, isolated hypogonadotropic hypogonadism is more typically associated with normal olfactory and GnRH neuronal development, but impaired regulation of GnRH secretion.33,35”
From Pubertal development and regulation (2016) · cites this paper as [33]
In the citing paper
“Impairment of the migration of these neurons is often associated with genetic defects.33–35”
From Pubertal development and regulation (2016) · cites this paper as [33]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Regulation of GnRH secretion > LEP and LEPR
“inactivating mutations in LEP58 or the gene encoding its receptor, LEPR,59”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > References
“58. Clément K A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction Nature 392 398 401 1998 9537324 59. Strobel A Issad T Camoin L Ozata M Strosberg AD A leptin missense mutation associated with hypogonadism and morbid obesity Nat Genet 18 213 215 1998 9500540”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > KAL1
“The KAL1 gene comprises 14 exons and encodes a 680 amino acid protein”
§ The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism > Migration of GnRH neurons > KAL1
“If expressed, this mutant anosmin 1 encodes a truncated protein that lacks 525 of its 610 amino acids.”
Citations
Cites
The GPR54 Gene as a Regulator of Puberty
Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa035322 · Cited by 2,557
Self-citationHypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54
de Roux, N., Genin, E., Carel, J.-C., Matsuda, F., Chaussain, J.-L., & Milgrom, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834399100 · Cited by 2,431 · cited 1×
“Regulation of GnRH secretion KISS1 and KISS1R The reproductive roles of the G-protein-coupled KiSS-1 receptor (also known as GPR54, encoded by KISS1R ) and its endogenous ligand, kisspeptin 1 (encoded by KISS1 ) were revealed in 2003 when inactivating mutations in the KiSS-1 receptor were found in the homozygous state…”
BackgroundA mutation in the human leptin receptor gene causes obesity and pituitary dysfunction
Clément, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., Gourmelen, M., Dina, C., Chambaz, J., Lacorte, J.-M., et al. (1998) · Nature · doi:10.1038/32911 · Cited by 2,346
Kotani, M., Detheux, M., Vandenbogaerde, A., Communi, D., Vanderwinden, J.-M., Le Poul, E., Brézillon, S., Tyldesley, R., Suarez-Huerta, N., Vandeput, F., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104847200 · Cited by 1,546
Chehab, F. F., Lim, M. E., & Lu, R. (1996) · Nature Genetics · doi:10.1038/ng0396-318 · Cited by 1,476
Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor
Ohtaki, T., Shintani, Y., Honda, S., Matsumoto, H., Hori, A., Kanehashi, K., Terao, Y., Kumano, S., Takatsu, Y., Masuda, Y., et al. (2001) · Nature · doi:10.1038/35079135 · Cited by 1,447
A role for kisspeptins in the regulation of gonadotropin secretion in the mouse
Gottsch, M. L., Cunningham, M. J., Smith, J. T., Popa, S. M., Acohido, B. V., Crowley, W. F., Seminara, S., Clifton, D. K., & Steiner, R. A. (2004) · Endocrinology · doi:10.1210/en.2004-0431 · Cited by 1,161
A leptin missense mutation associated with hypogonadism and morbid obesity
Strobel, A., Issad, T., Camoin, L., Ozata, M., & Strosberg, A. D. (1998) · Nature Genetics · doi:10.1038/ng0398-213 · Cited by 1,158
Jackson, R. S., Creemers, J. W. M., Ohagi, S., Raffin-Sanson, M.-L., Sanders, L., Montague, C. T., Hutton, J. C., & O'Rahilly, S. (1997) · Nature Genetics · doi:10.1038/ng0797-303 · Cited by 1,153
Topaloglu, A. K., Reimann, F., Guclu, M., Yalin, A. S., Kotan, L. D., Porter, K. M., Serin, A., Mungan, N. O., Cook, J. R., Ozbek, M. N., et al. (2009) · Nature Genetics · doi:10.1038/ng.306 · Cited by 961
Cited by
Sorted by citations
Krausz, C. G., & Riera‐Escamilla, A. (2018) · Nature Reviews Urology · doi:10.1038/s41585-018-0003-3 · Cited by 953
Boehm, U., Bouloux, P.-M., Dattani, M. T., de Roux, N., Dodé, C., Dunkel, L., Dwyer, A. A., Giacobini, P., Hardelin, J.-P., Juul, A., et al. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.112 · Cited by 874
Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., & Pollard, J. W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026317 · Cited by 649
Pubertal development and regulation
Abreu, A. P., & Kaiser, U. B. (2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00418-0 · Cited by 611
Self-citationCentral Precocious Puberty Caused by Mutations in the Imprinted Gene MKRN3
Abreu, A. P., Dauber, A., Macedo, D. B., Noel, S. D., Brito, V. N., Gill, J. C., Cukier, P., Thompson, I. R., Navarro, V. M., Gagliardi, P. C., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302160 · Cited by 534
Self-citationEisenberg, M. L., Esteves, S. C., Lamb, D. J., Hotaling, J. M., Giwercman, A., Hwang, K., & Cheng, Y.-S. (2023) · Nature Reviews Disease Primers · doi:10.1038/s41572-023-00459-w · Cited by 536
Male infertility: Pathogenesis and clinical diagnosis
Krausz, C. G. (2011) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.08.006 · Cited by 517
Control of puberty onset and fertility by gonadotropin-releasing hormone neurons
Herbison, A. E. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.70 · Cited by 515
Palmert, M. R., & Dunkel, L. (2012) · New England Journal of Medicine · doi:10.1056/nejmcp1109290 · Cited by 408
Oligogenic basis of isolated gonadotropin-releasing hormone deficiency
Sykiotis, G. P., Plummer, L., HUGHES, V. A., Au, M., Durrani, S., Nayak-Young, S., Dwyer, A. A., Quinton, R., Hall, J. E., Gusella, J. F., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009622107 · Cited by 371
Mutations of the KISS1 gene in disorders of puberty
Silveira, L. G., Noel, S. D., Silveira-Neto, A. P., Abreu, A. P., Brito, V. N., Santos, M. G., Bianco, S. D. C., Kuohung, W., Xu, S., Gryngarten, M., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2421 · Cited by 352
Self-citationMiraoui, H., Dwyer, A. A., Sykiotis, G. P., Plummer, L., Chung, W., Feng, B., Beenken, A., Clarke, J., Pers, T. H., Dworzynski, P., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.04.008 · Cited by 267
A genetic basis for functional hypothalamic amenorrhea
Caronia, L. M., Martin, C., Welt, C. K., Sykiotis, G. P., Quinton, R., Thambundit, A., Avbelj, M., Dhruvakumar, S., Plummer, L., Hughes, V. A., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa0911064 · Cited by 256
Hypogonadotropic Hypogonadism Revisited
Fraietta, R., Zylbersztejn, D. S., & Esteves, S. C. (2013) · Clinics · doi:10.6061/clinics/2013(sup01)09 · Cited by 250
Harrington, J., & Palmert, M. R. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1598 · Cited by 226
Guidelines on Male Infertility
Jungwirth, A., Diemer, T., Giwercman, A., Kopa, Z., Krausz, C. G., & Tournaye, H. J. (2012) · Cited by 221
A comprehensive review of genetics and genetic testing in azoospermia
Hamada, A., Esteves, S. C., & Agarwal, A. K. (2013) · Clinics · doi:10.6061/clinics/2013(sup01)06 · Cited by 202
Incidence, Phenotypic Features and Molecular Genetics of Kallmann Syndrome in Finland
Laitinen, E., Vaaralahti, K., Tommiska, J., Eklund, E., Tervaniemi, M. H., Valanne, L. K., & Raivio, T. (2011) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-6-41 · Cited by 200
Cangiano, B., Swee, D. S., Quinton, R., & Bonomi, M. (2020) · Human Genetics · doi:10.1007/s00439-020-02147-1 · Cited by 184
Santi, D., Crépieux, P., Reiter, É., Spaggiari, G., Brigante, G., Casarini, L., Rochira, V., & Simoni, M. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9041014 · Cited by 174
Raivio, T., Stefanija, M. A., McCabe, M. J., Romero, C. J., Dwyer, A. A., Tommiska, J., Sykiotis, G. P., Gregory, L. C., Diaczok, D., Tziaferi, V., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2938 · Cited by 169
Genetic basis and variable phenotypic expression of Kallmann syndrome: towards a unifying theory
Mitchell, A. L., Dwyer, A. A., Pitteloud, N., & Quinton, R. (2011) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2011.03.002 · Cited by 154
Neonatal gonadotropin therapy in male congenital hypogonadotropic hypogonadism
Bouvattier, C. M., Maione, L., Bouligand, J., Dodé, C., Guiochon‐Mantel, A., & Young, J. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.164 · Cited by 143
Reduced FSH and LH action: implications for medically assisted reproduction
Bosch, E., Alviggi, C., Lispi, M., Conforti, A., Hanyaloglu, A. C., Chuderland, D., Simoni, M., Raine‐Fenning, N., Crépieux, P., Kol, S., et al. (2021) · Human Reproduction · doi:10.1093/humrep/deab065 · Cited by 153
Howard, S. R., Guasti, L., Ruiz‐Babot, G., Mancini, A., David, A., Storr, H. L., Metherell, L., Sternberg, M. J. E., Cabrera, C., Warren, H. R., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606250 · Cited by 137
Epigenetic regulation of female puberty
Lomniczi, A., Wright, H., & Ojeda, S. R. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.08.003 · Cited by 136
Mutation in TDRD9 causes non-obstructive azoospermia in infertile men
Arafat, M., Har‐Vardi, I., Harlev, A., Levitas, E., Zeadna, A., Abofoul‐Azab, M., Dyomin, V., Sheffield, V. C., Lunenfeld, E., Huleihel, M., et al. (2017) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2017-104514 · Cited by 139
International consensus statement on allergy and rhinology: Olfaction
Patel, Z. M., Holbrook, E. H., Turner, J. H., Adappa, N. D., Albers, M. W., Altundağ, A., Appenzeller, S., Costanzo, R. M., Croy, I., Davis, G. E., et al. (2022) · International Forum of Allergy & Rhinology · doi:10.1002/alr.22929 · Cited by 142
A novel syndrome caused by the E410K amino acid substitution in the neuronal β-tubulin isotype 3
Chew, S., Balasubramanian, R., Chan, W. M., Kang, P. B., Andrews, C. V., Webb, B. D., MacKinnon, S. E., Oystreck, D. T., Rankin, J. K., Crawford, T. O., et al. (2013) · Brain · doi:10.1093/brain/aws345 · Cited by 126
A new pathway in the control of the initiation of puberty: the MKRN3 gene
Abreu, A. P., Macedo, D. B., Brito, V. N., Kaiser, U. B., & Latronico, A. C. (2015) · Journal of Molecular Endocrinology · doi:10.1530/jme-14-0315 · Cited by 126
Self-citationGenetic determinants of pubertal timing in the general population
Gajdos, Z. K. Z., Henderson, K. D., Hirschhorn, J. N., & Palmert, M. R. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.01.038 · Cited by 121
Yang, J. J., Caligioni, C. S., Chan, Y.-M., & Seminara, S. B. (2012) · Endocrinology · doi:10.1210/en.2011-1949 · Cited by 122
Sykiotis, G. P., Hoang, X.-H., Stefanija, M. A., Hayes, F. J., Thambundit, A., Dwyer, A. A., Au, M., Plummer, L., Crowley, W. F., & Pitteloud, N. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2582 · Cited by 121
Gonadotrophin replacement for induction of fertility in hypogonadal men
Dwyer, A. A., Raivio, T., & Pitteloud, N. (2015) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2014.10.005 · Cited by 114
Martin, C., Balasubramanian, R., Dwyer, A. A., Au, M., Sidis, Y., Kaiser, U. B., Seminara, S. B., Pitteloud, N., Zhou, Q., & Crowley, W. F. (2010) · Endocrine Reviews · doi:10.1210/er.2010-0007 · Cited by 114
Self-citationComing of age in the Kisspeptin Era: Sex differences, development, and puberty
Kauffman, A. S. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.01.017 · Cited by 106
Approach to the Male Patient with Congenital Hypogonadotropic Hypogonadism
Young, J. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1664 · Cited by 110
Leka-Emiri, S., Chrousos, G. P., & Kanaka‐Gantenbein, C. (2017) · Journal of Endocrinological Investigation · doi:10.1007/s40618-017-0627-9 · Cited by 103
BAX-Dependent and BAX-Independent Regulation of Kiss1 Neuron Development in Mice
Semaan, S. J., Murray, E. K., Poling, M. C., Dhamija, S., Forger, N. G., & Kauffman, A. S. (2010) · Endocrinology · doi:10.1210/en.2010-0783 · Cited by 107
Vosges, M., Page, Y. L., Chung, B., Combarnous, Y., Porcher, J., Kah, O., & Brion, F. (2010) · Aquatic Toxicology · doi:10.1016/j.aquatox.2010.06.009 · Cited by 98
Nasal Placode Development, GnRH Neuronal Migration and Kallmann Syndrome
Cho, H., Shan, Y., Whittington, N. C., & Wray, S. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00121 · Cited by 92
Isolated and syndromic forms of congenital anosmia
Karstensen, H. G., & Tommerup, N. (2011) · Clinical Genetics · doi:10.1111/j.1399-0004.2011.01776.x · Cited by 91
Molecular insights into the aetiology of female reproductive ageing
Perry, J. R. B., Murray, A., Day, F. R., & Ong, K. K. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.167 · Cited by 86
New understandings of the genetic basis of isolated idiopathic central hypogonadism
Bonomi, M., Libri, D. V., Guizzardi, F., Guarducci, E., Maiolo, E., Pignatti, E., Asci, R., & Persani, L. (2011) · Asian Journal of Andrology · doi:10.1038/aja.2011.68 · Cited by 85
Li, C., Han, T., Li, Q., Zhang, M., Guo, R., Yang, Y., Lü, W., Li, Z., Peng, C., Wu, P., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab155 · Cited by 85
Toro, C. A., Wright, H., Aylwin, C. F., Ojeda, S. R., & Lomniczi, A. (2017) · Nature Communications · doi:10.1038/s41467-017-02512-1 · Cited by 81
Deciphering Genetic Disease in the Genomic Era: The Model of GnRH Deficiency
Sykiotis, G. P., Pitteloud, N., Seminara, S. B., Kaiser, U. B., & Crowley, W. F. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3000288 · Cited by 80
Self-citationNeural Crest and Olfactory System: New Prospective
Forni, P. E., & Wray, S. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8286-5 · Cited by 84
Testosterone and Male Infertility
Ohlander, S. J., Lindgren, M. C., & Lipshultz, L. I. (2016) · Urologic Clinics of North America · doi:10.1016/j.ucl.2016.01.006 · Cited by 78
Bianco, S. D. C., Vandepas, L. E., Correa-Medina, M., Gereben, B., Mukherjee, A., Kuohung, W., Carroll, R. S., Teles, M. G., Latronico, A. C., & Kaiser, U. B. (2011) · Endocrinology · doi:10.1210/en.2010-0903 · Cited by 78
Self-citationMutation screening of SEMA3A and SEMA7A in patients with congenital hypogonadotropic hypogonadism
Känsäkoski, J., Fagerholm, R., Laitinen, E., Vaaralahti, K., Hackman, P., Pitteloud, N., Raivio, T., & Tommiska, J. (2014) · Pediatric Research · doi:10.1038/pr.2014.23 · Cited by 79
The Emerging Role of Epigenetics in the Regulation of Female Puberty
Lomniczi, A., & Ojeda, S. R. (2015) · Endocrine development · doi:10.1159/000438840 · Cited by 75
TRANSITION IN ENDOCRINOLOGY: Hypogonadism in adolescence
Dwyer, A. A., Phan-Hug, F., Hauschild, M., Elowe-Gruau, É., & Pitteloud, N. (2015) · European Journal of Endocrinology · doi:10.1530/eje-14-0947 · Cited by 75
Genetics of Isolated Hypogonadotropic Hypogonadism: Role of GnRH Receptor and Other Genes
Karges, B., Joseph, N., de Roux, N., & Karges, W. (2011) · International Journal of Endocrinology · doi:10.1155/2012/147893 · Cited by 73
Hypothalamic Dysregulation and Infertility in Mice Lacking the Homeodomain Protein Six6
Larder, R., Clark, D. D., Miller, N. L. G., & Mellon, P. L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1688-10.2011 · Cited by 73
FSH for the Treatment of Male Infertility
Casarini, L., Crépieux, P., Reiter, É., Lazzaretti, C., Paradiso, E., Rochira, V., Brigante, G., Santi, D., & Simoni, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072270 · Cited by 70
Teles, M. G., Silveira, L. F. G., Tusset, C., & Latronico, A. C. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.05.019 · Cited by 61
Genetics of Mammalian Reproduction: Modeling the End of the Germline
Matzuk, M. M., & Burns, K. H. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020911-153248 · Cited by 59
Beneduzzi, D., Trarbach, E. B., Min, L., Jorge, A. A. L., Garmes, H. M., Renck, A. C., Fichna, M., Fichna, P., Arantes, K. A., Costa, E. M. F., et al. (2014) · Fertility and Sterility · doi:10.1016/j.fertnstert.2014.05.044 · Cited by 57
Self-citationGonadal and Nongonadal Regulation of Sex Differences in Hypothalamic Kiss1 Neurones
Kauffman, A. S. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02030.x · Cited by 57
Recent advances in the genetics of testicular failure
Lamb, D., Song, S., Chiba, K., & Ramasamy, R. (2016) · Asian Journal of Andrology · doi:10.4103/1008-682x.178857 · Cited by 57
Taroc, E. Z. M., Prasad, A., Lin, J. M., & Forni, P. E. (2017) · Biology Open · doi:10.1242/bio.029074 · Cited by 58
Emerging Genetic and Epigenetic Mechanisms Underlying Pubertal Maturation in Adolescence
Aylwin, C. F., Toro, C. A., Shirtcliff, E. A., & Lomniczi, A. (2019) · Journal of Research on Adolescence · doi:10.1111/jora.12385 · Cited by 60
Arauz, R. F., Solomon, B. D., Pineda-Alvarez, D., Gropman, A., Parsons, J., Roessler, E., & Muenke, M. (2010) · Molecular Syndromology · doi:10.1159/000302285 · Cited by 52
Bianco, S. D. C. (2012) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00149 · Cited by 57
Self-citationMcClelland, K. S., Bell, K. M., Larney, C., Harley, V. R., Sinclair, A. H., Oshlack, A., Koopman, P. A., & Bowles, J. (2015) · Biology of Reproduction · doi:10.1095/biolreprod.115.128918 · Cited by 53
Deletion of Otx2 in GnRH Neurons Results in a Mouse Model of Hypogonadotropic Hypogonadism
Diaczok, D., DiVall, S. A., Matsuo, I., Wondisford, F. E., Wolfe, A., & Radovick, S. (2011) · Molecular Endocrinology · doi:10.1210/me.2010-0271 · Cited by 53
Wang, Y., Gong, C., Qin, M., Liu, Y., & Tian, Y. (2017) · Clinical Endocrinology · doi:10.1111/cen.13451 · Cited by 49
Reproductive tract function and dysfunction in women
Roy, A., & Matzuk, M. M. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.79 · Cited by 49
Dwyer, A. A., Quinton, R., Pitteloud, N., & Morin, D. (2014) · Sexual Medicine · doi:10.1002/sm2.50 · Cited by 46
Delayed puberty versus hypogonadism: a challenge for the pediatrician
Bozzola, M., Bozzola, E., Montalbano, C., Stamati, F. A., Ferrara, P., & Villani, A. (2018) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2018.23.2.57 · Cited by 46
Gonadotropin-Releasing Hormone Receptor (GnRHR) and Hypogonadotropic Hypogonadism
Fanis, P., Neocleous, V., Papapetrou, I., Phylactou, L. A., & Skordis, N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115965 · Cited by 45
G protein-coupled receptors involved in GnRH regulation: Molecular insights from human disease
Noel, S. D., & Kaiser, U. B. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.06.022 · Cited by 43
Self-citationSpilker, C., Nullmeier, S., Grochowska, K. M., Schumacher, A., Butnaru, I., Macharadze, T., Gomes, G. M., Yuanxiang, P., Bayraktar, G., Rodenstein, C., et al. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005907 · Cited by 43
Hou, H., Uusküla-Reimand, L., Makarem, M., Corre, C., Saleh, S., Metcalf, A., Goldenberg, A., Palmert, M. R., & Wilson, M. D. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx246 · Cited by 45
Looking for the bird Kiss: evolutionary scenario in sauropsids
Pasquier, J., Lafont, A.-G., Rousseau, K., Quérat, B., Chemineau, P., & Dufour, S. (2014) · BMC Evolutionary Biology · doi:10.1186/1471-2148-14-30 · Cited by 42
Kisspeptins and the control of gonadotrophin secretion
Dedes, I. (2012) · Systems Biology in Reproductive Medicine · doi:10.3109/19396368.2011.651555 · Cited by 43
Ye, P., Ge, K., Li, M., Yang, L., Jin, S., Zhang, C., Chen, X., & Geng, Z. (2019) · Poultry Science · doi:10.3382/ps/pez433 · Cited by 41
The Development of Kisspeptin Circuits in the Mammalian Brain
Semaan, S. J., Tolson, K. P., & Kauffman, A. S. (2013) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-6199-9_11 · Cited by 42
Gong, C., Liu, Y., Qin, M., Wu, D., & Wang, X. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1343 · Cited by 40
Li, F., Li, D., Liu, H., Cao, B., Jiang, F., Chen, D., & Li, J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00012 · Cited by 42
Advances in clinical applications of kisspeptin-GnRH pathway in female reproduction
Hu, K.-L., Chen, Z., Li, X., Cai, E., Yang, H., Chen, Y., Wang, C., Ju, L., Deng, W., & Mu, L. (2022) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-022-00953-y · Cited by 47
Prokineticins and their G protein-coupled receptors in health and disease
Zhao, Y., Wu, J., Wang, X., Jia, H., Chen, D., & Li, J. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2018.09.006 · Cited by 42
Molecular and Genetic Aspects of Congenital Isolated Hypogonadotropic Hypogonadism
Amato, L. G. L., Latronico, A. C., & Silveira, L. F. G. (2017) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2017.01.010 · Cited by 37
Neocleous, V., Fanis, P., Toumba, M., Tanteles, G. A., Schiza, M., Cinarli, F., Nicolaides, N. C., Oulas, A., Spyrou, G. M., Mantzoros, C. S., et al. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00626 · Cited by 35
KISS1R: Hallmarks of an Effective Regulator of the Neuroendocrine Axis
Millar, R. P., & Babwah, A. V. (2015) · Neuroendocrinology · doi:10.1159/000381457 · Cited by 36
Berghard, A., Hägglund, A., Bohm, S., & Carlsson, L. (2012) · The FASEB Journal · doi:10.1096/fj.12-206193 · Cited by 35
Hoffmann, H. M., Trang, C., Gong, P., Kimura, I., Pandolfi, E. C., & Mellon, P. L. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2723-15.2016 · Cited by 36
Zhao, Y., Wu, J., Jia, H., Wang, X., Zheng, R., Jiang, F., Chen, D., Chen, Z., & Li, J. (2018) · The FASEB Journal · doi:10.1096/fj.201801575r · Cited by 34
Fanis, P., Skordis, N., Toumba, M., Papaioannou, N. Y., Makris, A., Kyriakou, A., Neocleous, V., & Phylactou, L. A. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00677 · Cited by 36
Heterozygous Deletion of Ventral Anterior Homeobox (Vax1) Causes Subfertility in Mice
Hoffmann, H. M., Tamrazian, A., Xie, H., Millan, M. I. P., Kauffman, A. S., & Mellon, P. L. (2014) · Endocrinology · doi:10.1210/en.2014-1277 · Cited by 34
Genetic Overlap between Holoprosencephaly and Kallmann Syndrome
Vaaralahti, K., Raivio, T., Koivu, R., Valanne, L. K., Laitinen, E., & Tommiska, J. (2012) · Molecular Syndromology · doi:10.1159/000338706 · Cited by 35
Achermann, J. C., & Hughes, I. A. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-0324-5.00023-7 · Cited by 34
The olfactory bulb: A neuroendocrine spotlight on feeding and metabolism
Stark, R. (2024) · Journal of Neuroendocrinology · doi:10.1111/jne.13382 · Cited by 41
Al-Sayed, Y., & Howard, S. R. (2022) · European Journal of Human Genetics · doi:10.1038/s41431-022-01261-0 · Cited by 36
Shin, S.-J., Sul, Y., Kim, J. H., Cho, J. H., Kim, G.-H., Kim, J. H., Choi, J., & Yoo, H. (2015) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2015.20.1.27 · Cited by 32
Gürbüz, F., Kotan, L. D., Mengen, E., Şıklar, Z., Berberoğlu, M., Dökmetaş, H. S., Kılıçlı, M. F., Güven, A., Kırel, B., Saka, N., et al. (2012) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.725 · Cited by 30
The Metabolite GnRH-(1-5) Inhibits the Migration of Immortalized GnRH Neurons
Larco, D. O., Cho-Clark, M. J., Mani, S. K., & Wu, T. J. (2013) · Endocrinology · doi:10.1210/en.2012-1746 · Cited by 30
Advances in Genetic Diagnosis of Kallmann Syndrome and Genetic Interruption
Liu, Y., & Zhi, X. (2021) · Reproductive Sciences · doi:10.1007/s43032-021-00638-8 · Cited by 32
X-linked GnRH deficiency: Role of KAL-1 mutations in GnRH deficiency
Hu, Y., & Bouloux, P.-M. G. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.04.001 · Cited by 31
Metadata
- Authors
- Bianco, S. D. C., & Kaiser, U. B.
- Affiliations
- University of Miami (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Kaiser, Ursula B.
- Venue
- Nature Reviews Endocrinology
- Published
- 2009-08-25
- Volume
- 5
- Issue
- 10
- Pages
- 569-576
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- PMC
- PMC2864719
- OpenAlex
- W2051108558
- Semantic Scholar
- 334b3bd07e60cf46bd38933af90a2261a348376b
- Cited by
- 336
- References
- 77
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 18 · 2023: 20 · 2022: 31 · 2021: 22 · 2020: 16 · 2019: 22 · 2018: 17 · 2017: 21 · 2016: 14 · 2015: 20 · 2014: 22 · 2013: 24 · 2012: 21
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD019938, K12HD051959, HD028138, R01 HD051959, R21HD059015, U54HD028138)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Keywords
- idiopathic hypogonadotropic hypogonadism, Kallmann syndrome, anosmia, KAL1, FGFR1, prokineticin 2, PROKR2, GnRH receptor, KISS1R, TAC3, TACR3, nasal placode, hypothalamus, genetic mutations, molecular mechanisms
- MeSH terms
- Olfaction Disorders, Gastrointestinal Hormones, Humans, Hypogonadism, Nerve Tissue Proteins, Neuropeptides, Extracellular Matrix Proteins, Receptors, Peptide, Receptors, G-Protein-Coupled, Receptor, Fibroblast Growth Factor, Type 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
