Cited by 397Hypothalamic control of reproductive hormonesGenetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesFibroblast Growth Factor Research

The DOI matches its Crossref record; 58 of the 59 references it cites were found in a registry or an index.

Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice

Open access

Falardeau, John, Chung, Wilson C.J., Beenken, Andrew, Raivio, Taneli, Plummer, Lacey, Sidis, Yisrael, Jacobson-Dickman, Elka E., Eliseenkova, Anna V., Ma, Jinghong, Dwyer, Andrew, Quinton, Richard, Na, Sandra, Hall, Janet E., Huot, Celine, Alois, Natalie, Pearce, Simon H.S., Cole, Lindsay W., Hughes, Virginia, Mohammadi, Moosa, Tsai, Pei, Pitteloud, Nelly·2008·Journal of Clinical Investigation

DOI 10.1172/jci34538PMC PMC2441855

Open this paper in CoChat — free account Open PDF

Abstract

Idiopathic hypogonadotropic hypogonadism (IHH) with anosmia (Kallmann syndrome; KS) or with a normal sense of smell (normosmic IHH; nIHH) are heterogeneous genetic disorders associated with deficiency of gonadotropin-releasing hormone (GnRH). While loss-of-function mutations in FGF receptor 1 (FGFR1) cause human GnRH deficiency, to date no specific ligand for FGFR1 has been identified in GnRH neuron ontogeny. Using a candidate gene approach, we identified 6 missense mutations in FGF8 in IHH probands with variable olfactory phenotypes. These patients exhibited varied degrees of GnRH deficiency, including the rare adult-onset form of hypogonadotropic hypogonadism. Four mutations affected all 4 FGF8 splice isoforms (FGF8a, FGF8b, FGF8e, and FGF8f), while 2 mutations affected FGF8e and FGF8f isoforms only. The mutant FGF8b and FGF8f ligands exhibited decreased biological activity in vitro. Furthermore, mice homozygous for a hypomorphic Fgf8 allele lacked GnRH neurons in the hypothalamus, while heterozygous mice showed substantial decreases in the number of GnRH neurons and hypothalamic GnRH peptide concentration. In conclusion, we identified FGF8 as a gene implicated in GnRH deficiency in both humans and mice and demonstrated an exquisite sensitivity of GnRH neuron development to reductions in FGF8 signaling.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1172/jci34538

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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
Receptor Specificity of the Fibroblast Growth Factor Family
Ornitz, D. M., Xu, J., Colvin, J. S., McEwen, D. G., MacArthur, C. A., Coulier, F., Gao, G., & Goldfarb, M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.15292 · Cited by 1,871
Dynamics of gonadotropin-releasing hormone release during a pulse.
Moenter, S. M., Brand, R. M., MIDGLEY, A. R., & Karsch, F. J. (1992) · Endocrinology · doi:10.1210/endo.130.1.1727719 · Cited by 1,257
Crystal Structure of a Ternary FGF-FGFR-Heparin Complex Reveals a Dual Role for Heparin in FGFR Binding and Dimerization
Schlessinger, J., Plotnikov, A. N., Ibrahimi, O. A., Eliseenkova, A. V., Yeh, B. K., Yayon, A., Linhardt, R. J., & Mohammadi, M. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00073-3 · Cited by 1,199
Self-citation
The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo
Crossley, P. H., & Martin, G. R. (1995) · Development · doi:10.1242/dev.121.2.439 · Cited by 1,185
Receptor Specificity of the Fibroblast Growth Factor Family
Zhang, X., Ibrahimi, O. A., Olsen, S. K., Umemori, H., Mohammadi, M., & Ornitz, D. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601252200 · Cited by 1,164
Self-citation
An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination
Meyers, E., Lewandoski, M., & Martin, G. (1998) · Nature Genetics · doi:10.1038/ng0298-136 · Cited by 1,126
Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome
Dodé, C., Levilliers, J., Dupont, J., Paepe, A. D., Dû, N. L., Soussi‐Yanicostas, N., Coimbra, R. S., Delmaghani, S., Nouaille, S., Baverel, F., et al. (2003) · Nature Genetics · doi:10.1038/ng1122 · Cited by 839
Digenic Retinitis Pigmentosa Due to Mutations at the Unlinked Peripherin/ RDS and ROM1 Loci
Kajiwara, K., Berson, E. L., & Dryja, T. P. (1994) · Science · doi:10.1126/science.8202715 · Cited by 783
Structural basis for fibroblast growth factor receptor activation
Mohammadi, M., Olsen, S. K., & Ibrahimi, O. A. (2005) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2005.01.008 · Cited by 761
Self-citation

Flagged first, then by citations

Show all 59 references

1 of the 59 references couldn’t be matched to a known paper.

Research works printed but not linked: 5

Herbison, A.E. 2006. Physiology of the GnRH neuronal network. InKnobil and Neill’s physiology of reproduction. 3rd edition. J.D. Neill, editor. Academic Press. San Diego, California, USA. 1415–1482.
Finkelstein, 1987, Ann. Intern. Med., 104, 777
10.1210/jc.86.4.1532 · DOI
10.1210/jc.87.1.152 · DOI
10.1210/jc.84.3.1028 · DOI

Sorted by citations

Items 101–200 of 396

Clues to an early diagnosis of Kallmann syndrome
Kaplan, J. D., Bernstein, J. A., Hanson‐Kahn, A., & Hudgins, L. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33442 · Cited by 59
Evaluating CHARGE syndrome in congenital hypogonadotropic hypogonadism patients harboring CHD7 variants
Xu, C., Cassatella, D., van der Sloot, A. M., Quinton, R., Hauschild, M., Geyter, C. D., Flück, C. E., Feller, K., Bartholdi, D., Nemeth, A., et al. (2017) · Genetics in Medicine · doi:10.1038/gim.2017.197 · Cited by 59
Self-citation
The long-term clinical follow-up and natural history of men with adult-onset idiopathic hypogonadotropic hypogonadism
Dwyer, A. A., Hayes, F. J., Plummer, L., Pitteloud, N., & Crowley, W. F. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0245 · Cited by 58
Self-citation
Specification of GnRH-1 neurons by antagonistic FGF and retinoic acid signaling
Sabado, V., Barraud, P., Baker, C. V. H., & Streit, A. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.12.016 · Cited by 61
Pituitary Physiology and Diagnostic Evaluation
Melmed, S. K., Kleinberg, D. L., & Ho, K. K. Y. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-0324-5.00008-0 · Cited by 59
Kallmann syndrome with FGFR1 and KAL1 mutations detected during fetal life
Sarfati, J., Bouvattier, C. M., Bry‐Gauillard, H., Cartes, A., Bouligand, J., & Young, J. (2015) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-015-0287-9 · Cited by 57
A Hypomorphic Allele in the FGF8 Gene Contributes to Holoprosencephaly and Is Allelic to Gonadotropin-Releasing Hormone Deficiency in Humans
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
The role of fibroblast growth factor 8 in cartilage development and disease
Chen, H., Cui, Y., Zhang, D., Xie, J., & Zhou, X. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17174 · Cited by 54
When Genetic Load Does Not Correlate with Phenotypic Spectrum: Lessons from the GnRH Receptor (GNRHR)
Gianetti, E., Hall, J. E., Au, M. G., Kaiser, U. B., Quinton, R., Stewart, J. A., Metzger, D. L., Pitteloud, N., Mericq, V., Merino, P. M., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1264 · Cited by 53
Self-citation
Congenital Disorders of Deficiency in Glycosaminoglycan Biosynthesis
Mizumoto, S., & Yamada, S. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.717535 · Cited by 58
Underlying genetic factors of the VATER/VACTERL association with special emphasis on the “Renal” phenotype
Reutter, H. M., Hilger, A. C., Hildebrandt, F., & Ludwig, M. Z. (2016) · Pediatric Nephrology · doi:10.1007/s00467-016-3335-3 · Cited by 51
Fibroblast growth factor signaling in the developing neuroendocrine hypothalamus
Tsai, P., Brooks, L. R., Rochester, J. R., Kavanaugh, S. I., & Chung, W. C. J. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2010.11.002 · Cited by 52
Self-citation
The Indirect Role of Fibroblast Growth Factor-8 in Defining Neurogenic Niches of the Olfactory/GnRH Systems
Forni, P. E., Bharti, K., Flannery, E., Shimogori, T., & Wray, S. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3238-13.2013 · Cited by 50
Dominant-negative kinase domain mutations inFGFR1can explain the clinical severity of Hartsfield syndrome
Hong, S., Hu, P., Marino, J., Hufnagel, S. B., Hopkin, R. J., Toromanović, A., Richieri‐Costa, A., Ribeiro, L. A., Kruszka, P. S., Roessler, E., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw064 · Cited by 51
Clinical and genetic features of 64 young male paediatric patients with congenital hypogonadotropic hypogonadism
Wang, Y., Gong, C., Qin, M., Liu, Y., & Tian, Y. (2017) · Clinical Endocrinology · doi:10.1111/cen.13451 · Cited by 49
GnRH Neuronal Migration and Olfactory Bulb Neurite Outgrowth Are Dependent on FGF Receptor 1 Signaling, Specifically via the PI3K p110α Isoform in Chick Embryo
Hu, Y., Poopalasundaram, S., Graham, A., & Bouloux, P.-M. G. (2012) · Endocrinology · doi:10.1210/en.2012-1555 · Cited by 47
Quantitative Magnetic Resonance Imaging Evaluation of the Olfactory System in Kallmann Syndrome: Correlation with a Clinical Smell Test
Santos, M. K., Santos, A. C., Versiani, B. R., Diniz, P. R. B., Elías, J., & de Castro, M. (2011) · Neuroendocrinology · doi:10.1159/000328437 · Cited by 49
The genetic basis of female reproductive disorders: Etiology and clinical testing
Layman, L. C. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.02.016 · Cited by 48
Defective signaling through plexin-A1 compromises the development of the peripheral olfactory system and neuroendocrine reproductive axis in mice
Marcos, S., Monnier, C., Rovira, X., Fouveaut, C., Pitteloud, N., Ango, F., Dodé, C., & Hardelin, J. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx080 · Cited by 49
Self-citation
The Adhesion Molecule KAL-1/anosmin-1 Regulates Neurite Branching through a SAX-7/L1CAM–EGL-15/FGFR Receptor Complex
Díaz-Balzac, C. A., Lázaro‐Peña, M. I., Ramos-Ortiz, G. A., & Bülow, H. E. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.057 · Cited by 44
Combined pituitary hormone deficiency: current and future status
Castinetti, F., Reynaud, R., Quentien, M. H., Jullien, N., Marquant, E., Rochette, C., Herman, J. P., Saveanu, A., Barlier, A., Enjalbert, A., et al. (2014) · Journal of Endocrinological Investigation · doi:10.1007/s40618-014-0141-2 · Cited by 45
Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells
Lund, C., Pulli, K., Yellapragada, V., Giacobini, P., Lundin, K., Vuoristo, S., Tuuri, T., Noisa, P., & Raivio, T. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.06.007 · Cited by 47
Self-citation
Congenital hypogonadotropic hypogonadism in females: Clinical spectrum, evaluation and genetics
Bry‐Gauillard, H., Trabado, S., Bouligand, J., Sarfati, J., Francou, B., Salenave, S., Chanson, P., Brailly‐Tabard, S., Guiochon‐Mantel, A., & Young, J. (2010) · Annales d Endocrinologie · doi:10.1016/j.ando.2010.02.024 · Cited by 43
A broad range of ophthalmologic anomalies is part of the holoprosencephaly spectrum
Pineda‐Alvarez, D., Solomon, B. D., Roessler, E., Balog, J. Z., Hadley, D. W., Zein, W. M., Hadsall, C. K., Brooks, B. P., & Muenke, M. (2011) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.34261 · Cited by 43
The kisspeptin signaling pathway and its role in human isolated GnRH deficiency
Wahab, F., Quinton, R., & Seminara, S. B. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.05.043 · Cited by 43
Self-citation
FGFR1 Mutations in Kallmann Syndrome
Villanueva, C., & de Roux, N. (2010) · Frontiers of hormone research · doi:10.1159/000312693 · Cited by 43
Role of Fibroblast Growth Factor Signaling in Gonadotropin-Releasing Hormone Neuronal System Development
Chung, W. C. J., & Tsai, P. (2010) · Frontiers of hormone research · doi:10.1159/000312692 · Cited by 47
Self-citation
Reproductive endocrine phenotypes relating to CHD7 mutations in humans
Balasubramanian, R., & Crowley, W. F. (2017) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31585 · Cited by 44
Regulation of Temporal and Spatial Organization of Newborn GnRH Neurons by IGF Signaling in Zebrafish
Onuma, T. A., Ding, Y., Abraham, E., Zohar, Y., Ando, H., & Duan, C. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6804-10.2011 · Cited by 40
Genetic counseling for isolated GnRH deficiency
Au, M., Crowley, W. F., & Buck, C. L. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.05.041 · Cited by 40
An ancient founder mutation in PROKR2 impairs human reproduction
Stefanija, M. A., Jeanpierre, M., Sykiotis, G. P., Young, J., Quinton, R., Abreu, A. P., Plummer, L., Au, M., Balasubramanian, R., Dwyer, A. A., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds264 · Cited by 39
Self-citation
RNF216 Regulates the Migration of Immortalized GnRH Neurons by Suppressing Beclin1-Mediated Autophagy
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
Evidence for a Common Genetic Origin of Classic and Milder Adult-Onset Forms of Isolated Hypogonadotropic Hypogonadism
Cangiano, B., Duminuco, P., Vezzoli, V., Guizzardi, F., Chiodini, I., Corona, G., Maggi, M., Persani, L., & Bonomi, M. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8010126 · Cited by 40
Pituitary Physiology and Diagnostic Evaluation
Kaiser, U. B., & Ho, K. K. Y. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-29738-7.00008-3 · Cited by 39
The best-laid plans go oft awry: synaptogenic growth factor signaling in neuropsychiatric disease
Williams, A. J., & Umemori, H. (2014) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2014.00004 · Cited by 38
Regulation of FGF signaling: Recent insights from studying positive and negative modulators
Korsensky, L., & Ron, D. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.01.023 · Cited by 39
Evidence that FGFR1 loss-of-function mutations may cause variable skeletal malformations in patients with Kallmann syndrome
Jarząbek, K., Wołczyński, S., Lesniewicz, R., Plessis, G., & Kottler, M. (2012) · Advances in Medical Sciences · doi:10.2478/v10039-012-0036-4 · Cited by 39
Novel insights in FGFR1 regulation: lessons from Kallmann syndrome
Hu, Y., & Bouloux, P.-M. G. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.01.004 · Cited by 39
Isolated hypogonadotropic hypogonadism with SOX2 mutation and anophthalmia/microphthalmia in offspring
Stark, Z., Storen, R., Bennetts, B., Savarirayan, R., & Jamieson, R. V. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2011.11 · Cited by 36
Kallmann syndrome in women: from genes to diagnosis and treatment
Męczekalski, B., Podfigurna-Stopa, A., Smolarczyk, R., Katulski, K., & Genazzani, A. R. (2013) · Gynecological Endocrinology · doi:10.3109/09513590.2012.752459 · Cited by 37
Greater prevalence of PROKR2 mutations in Kallmann syndrome patients from the Maghreb than in European patients
Sarfati, J., Fouveaut, C., Leroy, C., Jeanpierre, M., Hardelin, J., & Dodé, C. (2013) · European Journal of Endocrinology · doi:10.1530/eje-13-0419 · Cited by 38
Signaling Pathways in Craniofacial Development
Neben, C. L., & Merrill, A. E. (2015) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2015.09.005 · Cited by 36
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
Translating genomics to the clinical diagnosis of disorders/differences of sex development
Parivesh, A., Barseghyan, H., Délot, E. C., & Vilain, E. J. N. (2019) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2019.01.005 · Cited by 37
Genetics of hypogonadotropic Hypogonadism—Human and mouse genes, inheritance, oligogenicity, and genetic counseling
Louden, E. D., Poch, A., Kim, H., Ben‐Mahmoud, A., Kim, S., & Layman, L. C. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111334 · Cited by 34
A histochemical study on condylar cartilage and glenoid fossa during mandibular advancement
Owtad, P., Potres, Z., Shen, G., Petocz, P., & Darendeliler, M. A. (2011) · The Angle Orthodontist · doi:10.2319/021710-99.1 · Cited by 33
Puberty
Witchel, S. F., & Topaloglu, A. K. (2019) · Elsevier eBooks · doi:10.1016/b978-0-323-47912-7.00017-2 · Cited by 42
The Role of Prokineticins in the Pathogenesis of Hypogonadotropic Hypogonadism
Abreu, A. P., Kaiser, U. B., & Latronico, A. C. (2010) · Neuroendocrinology · doi:10.1159/000308880 · Cited by 36
Sirt1-Deficient Mice Have Hypogonadotropic Hypogonadism due to Defective GnRH Neuronal Migration
Sante, G. D., Wang, L., Wang, C., Jiao, X., Casimiro, M. C., Chen, K., Pestell, T. G., Yaman, İ., Rocco, A. D., Sun, X., et al. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1228 · Cited by 37
Identification of differentially expressed genes in early inner ear development
Paxton, C. N., Bleyl, S. B., Chapman, S. C., & Schoenwolf, G. C. (2009) · Gene Expression Patterns · doi:10.1016/j.gep.2009.11.002 · Cited by 34
The Differential Roles for Neurodevelopmental and Neuroendocrine Genes in Shaping GnRH Neuron Physiology and Deficiency
Oleari, R., Massa, V., Cariboni, A. M., & Lettieri, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179425 · Cited by 36
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
Self-citation
Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways
Choy, C. T., Kim, H., Lee, J., Williams, D. M., Palethorpe, D., Fellows, G., Wright, A. J., Laing, K. G., Bridges, L., Howe, F. A., et al. (2013) · Endocrine Related Cancer · doi:10.1530/erc-13-0181 · Cited by 33
Fgf8a mutation affects craniofacial development and skeletal gene expression in zebrafish larvae
Gebuijs, I. G. E., Raterman, S. T., Metz, J. R., Swanenberg, L., Zethof, J., van den Bos, R., Carels, C. E. L., Wagener, F. A. D. T. G., & den Hoff, J. W. V. (2019) · Biology Open · doi:10.1242/bio.039834 · Cited by 33
Genetics of hypogonadotropic hypogonadism
Millar, A. C., Faghfoury, H., & Bieniek, J. M. (2021) · Translational Andrology and Urology · doi:10.21037/tau.2020.03.33 · Cited by 35
Discovering genes essential to the hypothalamic regulation of human reproduction using a human disease model: adjusting to life in the “-omics” era
Stamou, M. I., Cox, K. H., & Crowley, W. F. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1045.2016.1.test · Cited by 32
Olfactory System and Demyelination
García‐González, D., Murcia‐Belmonte, V., Clemente, D., & Castro, F. D. (2013) · The Anatomical Record · doi:10.1002/ar.22736 · Cited by 31
Characterization of the human GnRH neuron developmental transcriptome using a GNRH1 -TdTomato reporter line in human pluripotent stem cells
Lund, C., Yellapragada, V., Vuoristo, S., Balboa, D., Trova, S., Allet, C., Eskici, N., Pulli, K., Giacobini, P., Tuuri, T., et al. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.040105 · Cited by 32
Self-citation
PROKR2 and PROK2 mutations cause isolated congenital anosmia without gonadotropic deficiency
Moya‐Plana, A., Villanueva, C., Laccourreye, O., Bonfils, P., & de Roux, N. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0578 · Cited by 32
Cell migration in the developing rodent olfactory system
Huilgol, D., & Tole, S. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2172-7 · Cited by 34
The Adhesion Molecule Anosmin-1 in Neurology: Kallmann Syndrome and Beyond
de Castro, F., Esteban, P. F., Bribián, A., Murcia‐Belmonte, V., García‐González, D., & Clemente, D. (2013) · Advances in neurobiology · doi:10.1007/978-1-4614-8090-7_12 · Cited by 31
Shaping the Reproductive System: Role of Semaphorins in Gonadotropin-Releasing Hormone Development and Function
Giacobini, P. (2015) · Neuroendocrinology · doi:10.1159/000431021 · Cited by 32
Targeted Gene Panel Sequencing for Molecular Diagnosis of Kallmann Syndrome and Normosmic Idiopathic Hypogonadotropic Hypogonadism
Kim, J. H., Seo, G. H., Kim, G.-H., Huh, J., Hwang, I. T., Jang, J., Yoo, H., & Choi, J. (2018) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-0681-6608 · Cited by 30
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
Receptor Tyrosine Kinase Signaling
Fantauzzo, K. A., & Soriano, P. M. (2015) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2014.11.005 · Cited by 30
Screening of autosomal gene deletions in patients with hypogonadotropic hypogonadism using multiplex ligation‐dependent probe amplification: detection of a hemizygosis for the fibroblast growth factor receptor 1
Trarbach, E. B., Teles, M. G., Costa, E. M. F., Abreu, A. P., Garmes, H. M., Guerra‐Júnior, G., Baptista, M. T. M., de Castro, M., Mendonca, B. B., & Latronico, A. C. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03642.x · Cited by 29
Predicted mechanistic impacts of human protein missense variantsPreprint
Jänes, J., Müller, M., Selvaraj, S., Manoel, D., Stephenson, J. D., Gonçalves, C. I., Lafita, A., Polacco, B. J., Obernier, K., Alasoo, K., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.29.596373 · Cited by 27
Role of fibroblast growth factor (FGF) signaling in the neuroendocrine control of human reproduction
Miraoui, H., Dwyer, A. A., & Pitteloud, N. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.05.042 · Cited by 32
Self-citation
Pontocerebellar Hypoplasia: Review of Classification and Genetics, and Exclusion of Several Genes Known to Be Important for Cerebellar Development
Maricich, S. M., Aqeeb, K. A., Moayedi, Y., Mathes, E. L., Patel, M. S., Chitayat, D. A., Lyon, G., Leroy, J. G., & Zoghbi, H. Y. (2011) · Journal of Child Neurology · doi:10.1177/0883073810380047 · Cited by 28
Gonadotropin-releasing hormone neuron development in vertebrates
Duan, C., & Allard, J. B. (2020) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2020.113465 · Cited by 29
Pathology or Normal Variant: What Constitutes a Delay in Puberty?
Villanueva, C., & Argente, J. (2014) · Hormone Research in Paediatrics · doi:10.1159/000362600 · Cited by 28
Responsiveness to a Physiological Regimen of GnRH Therapy and Relation to Genotype in Women With Isolated Hypogonadotropic Hypogonadism
Abel, B. S., Shaw, N. D., Brown, J. M., Adams, J. M., Alati, T., Martin, K. A., Pitteloud, N., Seminara, S. B., Plummer, L., Pignatelli, D., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3294 · Cited by 26
Self-citation
Genotypic and phenotypic spectra of FGFR1, FGF8, and FGF17 mutations in a Chinese cohort with idiopathic hypogonadotropic hypogonadism
Men, M., Wu, J., Zhao, Y., Xing, X., Jiang, F., Zheng, R., & Li, J. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2019.08.069 · Cited by 27
NELF is a nuclear protein involved in hypothalamic GnRH neuronal migration
Xu, N., Bhagavath, B., Kim, H., Halvorson, L. M., Podolsky, R. H., Chorich, L. P., Prasad, P. D., Xiong, W., Cameron, R. S., & Layman, L. C. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.11.016 · Cited by 26
Molecular causes of hypogonadotropic hypogonadism
Topaloglu, A. K., & Kotan, L. D. (2010) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0b013e32833bb425 · Cited by 27
Expanding the Phenotypic Spectrum and Variability of Endocrine Abnormalities Associated With TUBB3 E410K Syndrome
Balasubramanian, R., Chew, S., MacKinnon, S. E., Kang, P. B., Andrews, C. V., Chan, W. M., & Engle, E. C. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-4107 · Cited by 26
Whole‐genome sequencing analysis in fetal structural anomalies: novel phenotype–genotype discoveries
Qi, Q., Jiang, Y., Zhou, X., Lü, Y., Xiao, R., Bai, J., Lou, H., Sun, W., Lian, Y., Hao, N., et al. (2023) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.27517 · Cited by 26
Genetics of congenital hypogonadotropic hypogonadism in Denmark
Tommiska, J., Känsäkoski, J., Christiansen, P., Jørgensen, N., Lawaetz, J. G., Juul, A., & Raivio, T. (2014) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2014.04.002 · Cited by 26
Self-citation
Numerous isoforms of Fgf8 reflect its multiple roles in the developing brain
Sunmonu, N. A., Li, K., & Li, J. Y. H. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22587 · Cited by 25
Neurobiology of puberty and its disorders
Witchel, S. F., & Plant, T. M. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-820683-6.00033-6 · Cited by 25
Genetic architecture of self-limited delayed puberty and congenital hypogonadotropic hypogonadism
Vezzoli, V., Hrvat, F., Goggi, G., Federici, S., Cangiano, B., Quinton, R., Persani, L., & Bonomi, M. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1069741 · Cited by 25
Self-citation
Lateralization of motor control in the human nervous system: genetics of mirror movements
Peng, J., & Charron, F. (2012) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2012.08.007 · Cited by 27
Normosmic idiopathic hypogonadotropic hypogonadism due to a novel homozygous nonsense c.C969A (p.Y323X) mutation in the KISS 1R gene in three unrelated families
Demirbilek, H., Özbek, M. N., Demir, K., Kotan, L. D., Cesur, Y., Doğan, M., Temiz, F., Mengen, E., Gürbüz, F., Yüksel, B., et al. (2014) · Clinical Endocrinology · doi:10.1111/cen.12618 · Cited by 25
Diseases of the Hypothalamus and the Pituitary Gland
Behre, H. M., Nieschlag, E., Partsch, C., Wieacker, P. F., & Simoni, M. (2010) · Springer eBooks · doi:10.1007/978-3-540-78355-8_12 · Cited by 25
Genetics of Male Infertility
Krausz, C. G., Rosta, V., Swerdloff, R. S., & Wang, C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-815236-2.00010-2 · Cited by 24
Invertebrate Models of Kallmann Syndrome: Molecular Pathogenesis and New Disease Genes
Schiavi, E. D., & Andrenacci, D. (2013) · Current Genomics · doi:10.2174/138920213804999174 · Cited by 24
Foxo1 Is Required for Normal Somatotrope Differentiation
Kapali, J., Kabat, B. E., Schmidt, K. L., Stallings, C. E., Tippy, M. D., Jung, D. O., Edwards, B. S., Nantie, L. B., Raeztman, L. T., Navratil, A. M., et al. (2016) · Endocrinology · doi:10.1210/en.2016-1372 · Cited by 23
Congenital Hypogonadotropic Hypogonadism with Anosmia and Gorlin Features Caused by a PTCH1 Mutation Reveals a New Candidate Gene for Kallmann Syndrome
Barraud, S., Delemer, B., Poirsier-Violle, C., Bouligand, J., Mérol, J., Grange, F., Higel-Chaufour, B., Decoudier, B., Zalzali, M., Dwyer, A. A., et al. (2020) · Neuroendocrinology · doi:10.1159/000506640 · Cited by 24
Self-citation
Genetics of congenital central hypogonadism
Grinspon, R. P. (2021) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2021.101599 · Cited by 21
Heterozygous FGF8 mutations in patients presenting cryptorchidism and multiple VATER/VACTERL features without limb anomalies
Zeidler, C., Woelfle, J., Draaken, M., Mughal, S. S., Große, G., Hilger, A. C., Dworschak, G. C., Boemers, T. M., Jenetzky, E., Zwink, N., et al. (2014) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.23278 · Cited by 21
CHAPTER 7 – Neuroendocrine Control of the Menstrual Cycle
Hall, J. (2009) · Elsevier eBooks · doi:10.1016/b978-1-4160-4907-4.00007-3 · Cited by 9
Self-citation
Compound Deficiencies in Multiple Fibroblast Growth Factor Signalling Components Differentially Impact the Murine Gonadotrophin‐Releasing Hormone System
Chung, W. C. J., Matthews, T. A., Tata, B. K., & Tsai, P. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02024.x · Cited by 26
Self-citation
NELF knockout is associated with impaired pubertal development and subfertility
Quaynor, S. D., Ko, E. K., Chorich, L. P., Sullivan, M. E., Demir, D., Waller, J. L., Kim, H.-G., Cameron, R. S., & Layman, L. C. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.02.015 · Cited by 20
Bi-allelic Pathogenic Variants in HS2ST1 Cause a Syndrome Characterized by Developmental Delay and Corpus Callosum, Skeletal, and Renal Abnormalities
Schneeberger, P. E., von Elsner, L., Barker, E. L., Meinecke, P., Marquardt, I., Alawi, M., Steindl, K., Joset, P., Rauch, A. M., Zwijnenburg, P. J. G., et al. (2020) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.10.007 · Cited by 21
Mouse models to study the central regulation of puberty
Colledge, W. H., Mei, H., & de Tassigny, X. D. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.01.015 · Cited by 20
Loss-of-function mutations in FGF8 can be independent risk factors for holoprosencephaly
Hong, S., Hu, P., Roessler, E., Hu, T., & Muenke, M. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy106 · Cited by 20
The Regulation and Function of Fibroblast Growth Factor 8 and Its Function during Gonadotropin-Releasing Hormone Neuron Development
Chung, W. C. J., Linscott, M. L., Rodriguez, K. M., & Stewart, C. E. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00114 · Cited by 22
Self-citation
Physiological Characterization and Transcriptomic Properties of GnRH Neurons Derived From Human Stem Cells
Keen, K. L., Petersen, A. J., Figueroa, A. G., Fordyce, B. I., Shin, J., Yadav, R., Erdin, S., Pearce, R. A., Talkowski, M. E., Bhattacharyya, A., et al. (2021) · Endocrinology · doi:10.1210/endocr/bqab120 · Cited by 19
Novel application of luciferase assay for the in vitro functional assessment of KAL1 variants in three females with septo-optic dysplasia (SOD)
McCabe, M. J., Hu, Y., Gregory, L. C., Gaston‐Massuet, C., Alatzoglou, K. S., Saldanha, J. W., Gualtieri, A., Thankamony, A., Hughes, I. A., Townshend, S., et al. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.09.010 · Cited by 20
Submicroscopic deletion involving the fibroblast growth factor receptor 1 gene in a patient with combined pituitary hormone deficiency
Fukami, M., Iso, M., Sato, N. S., Igarashi, M., Seo, M. K., Kazukawa, I., Kinoshita, E., Dateki, S., & Ogata, T. (2013) · Endocrine Journal · doi:10.1507/endocrj.ej13-0023 · Cited by 19

Authors: Falardeau, J., Chung, W. C. J., Beenken, A., Raivio, T., Plummer, L., Sidis, Y., Jacobson-Dickman, E. E., Eliseenkova, A. V., Ma, J., Dwyer, A., Quinton, R., Na, S., Hall, J. E., Huot, C., Alois, N., Pearce, S. H. S., Cole, L. W., Hughes, V., Mohammadi, M., Tsai, P., & Pitteloud, N.
Affiliations: Harvard University (US)
University of Colorado Boulder (US)
New York University (US)
Newcastle University (GB)
Centre Hospitalier Universitaire Sainte-Justine (CA)
Corresponding author: Pitteloud, Nelly
ORCID: Chung, Wilson C.J.
Beenken, Andrew
Raivio, Taneli
Jacobson-Dickman, Elka E.
Ma, Jinghong
Dwyer, Andrew
Quinton, Richard
Hall, Janet E.
Pearce, Simon H.S.
Mohammadi, Moosa
Tsai, Pei
Pitteloud, Nelly
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2008-08-01
Volume: 118
Issue: 8
Pages: 2822-2831
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci34538
PMC: PMC2441855
OpenAlex: W2101121629
Cited by: 397
References: 59
Citations by year: 2026: 4 · 2025: 8 · 2024: 11 · 2023: 11 · 2022: 17 · 2021: 16 · 2020: 17 · 2019: 24 · 2018: 13 · 2017: 19 · 2016: 28 · 2015: 27 · 2014: 27 · 2013: 32 · 2012: 25
FWCI: 44.77
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Newcastle University ePrints (Newcastle Univesity)
Funders: Lastentautien Tutkimussäätiö
Helsingin Sanomain Säätiö
National Institutes of Health
National Institute of Dental and Craniofacial Research (R01DE013686, R01 DE13686-08)
National Center for Research Resources (M01RR001066)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD015788, R01HD042708, U54HD028138)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Keywords: FGF8, FGF8b, gonadotropin-releasing hormone deficiency, idiopathic hypogonadotropic hypogonadism, Kallmann syndrome, anosmia, hypothalamus, FGF signaling, missense mutations
MeSH terms: Adult, Animals, Olfaction Disorders, Female, Heterozygote, Humans, Hypogonadism, Gonadotropin-Releasing Hormone, Male, Mice, Transgenic, Models, Molecular, Mutation, Neurons, Pedigree, Cohort Studies, Signal Transduction, Case-Control Studies, Kallmann Syndrome, Mice, Fibroblast Growth Factor 8

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.

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

Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks