A novel mutation L260P of the steroidogenic acute regulatory protein gene in three unrelated patients of Swiss ancestry with congenital lipoid adrenal hyperplasia
Abstract
CONTEXT: Lipoid congenital adrenal hyperplasia (CAH) is the most severe form of CAH leading to impaired production of all adrenal and gonadal steroids. Mutations in the gene encoding steroidogenic acute regulatory protein (StAR) cause lipoid CAH. OBJECTIVE: We investigated three unrelated patients of Swiss ancestry who all carried novel mutations in the StAR gene. All three subjects were phenotypic females with absent Müllerian derivatives, 46,XY karyotype, and presented with adrenal failure. METHODS AND RESULTS: StAR gene analysis showed that one patient was homozygous and the other two were heterozygous for the novel missense mutation L260P. Of the heterozygote patients, one carried the novel missense mutation L157P and one had a novel frameshift mutation (629-630delCT) on the second allele. The functional ability of all three StAR mutations to promote pregnenolone production was severely attenuated in COS-1 cells transfected with the cholesterol side-chain cleavage system and mutant vs. wild-type StAR expression vectors. CONCLUSIONS: These cases highlight the importance of StAR-dependent steroidogenesis during fetal development and early infancy; expand the geographic distribution of this condition; and finally establish a new, prevalent StAR mutation (L260P) for the Swiss population.
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The incidence of certain mutations is very high in specific ethnic groups.
“The incidence of certain mutations is very high in specific ethnic groups.”
From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [11]
The Discussion (page unavailable) identifies StAR mutation clusters in Japanese, Korean, Palestinian Arab, and eastern Saudi Arabian populations, and calls L260P a prevalent mutation among Swiss patients. It also says StAR defects are rare and gives no incidence showing that these mutations are very common within those populations. The 31% figure in Microsatellite analysis refers to a linked marker, not the mutation. (LLM, conf=0.85)
Experimental — accuracy not yet measuredLipoid CAH has been reported in most ethnic groups but is common among the Japanese, Korean, and Palestinian Arab populations.
“Lipoid CAH has been reported in most ethnic groups but is common among the Japanese, Korean, and Palestinian Arab populations1,3,4,10,11,13,29,30,31,32).”
From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [11]
The Abstract (page unavailable) says reported patients were predominantly from Japan, Korea, and Arabic countries; the Discussion (page unavailable) identifies mutation clusters in Japanese, Korean, and Palestinian Arab populations. These passages support the population pattern, but the paper does not say lipoid CAH has been reported in most ethnic groups. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLipoid CAH is common in Japan and Korea.
“Lipoid CAH is the most fatal form of CAH and is common in Japan and Korea.”
From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [11]
The introductory passage says reported patients were predominantly from Japan, Korea, and Arabic countries, and the Discussion identifies a mutation cluster in Japanese and Korean populations. But the Discussion also says StAR defects are rare and usually sporadic; the paper does not establish that lipoid CAH is common in Japan or Korea in an absolute sense. (LLM, conf=0.85)
Experimental — accuracy not yet measuredMost patients with lipoid CAH have evidence of salt loss in the first year of life, usually within the first 2 months.
“have evidence of salt loss in the first year of life and usually within the first 2 months3,4,10,11,12,13).”
From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [11]
The introduction says patients with lipoid CAH present with adrenal failure in infancy, and the Case reports describe salt wasting or adrenal insufficiency during the first year. But the Discussion places symptom onset in these patients at 2.5–5.5 months; the paper does not establish that salt loss usually occurs within the first two months. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAffected patients typically present with signs of severe adrenal failure in early infancy.
“Affected patients typically present with signs of severe adrenal failure in early infancy”
From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [11]
Most patients with lipoid CAH have female external genitalia regardless of chromosomal sex.
“Most patients have female external genitalia regardless of chromosomal sex”
From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [11]
The p.L260P mutation is in the Swiss population.
“and the p.L260P mutation in the Swiss population11).”
From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [11]
Other genetic clusters of lipoid CAH are found among Palestinian Arabs carrying R182L, in eastern Saudi Arabia carrying R182H, and in parts of Switzerland carrying L260P.
“Other genetic clusters are found among Palestinian Arabs, most of whom carry the mutation R182L (67); in eastern Saudi Arabia, carrying R182H (108); and in parts of Switzerland, carrying the mutation L260P (114).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [114]
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References 18 · Cited by 59
- Authors
- Flück, C. E., Maret, A., Mallet, D., Portrat-Doyen, S., Achermann, J. C., Leheup, B., Theintz, G. E., Mullis, P. E., & Morel, Y.
- Affiliations
- University of Bern (CH)
- Centre Hospitalier Universitaire Vaudois (CH)
- Lyon 1 Université (FR)
- University College London (GB)
- Centre Hospitalier Régional et Universitaire de Nancy (FR)
- Corresponding author
- Morel, Yves
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2005-09
- Volume
- 90
- Issue
- 9
- Pages
- 5304-5308
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2004341431
- Semantic Scholar
- 97551d1d673b790fb7cb2641e93ad549da824028
- Cited by
- 59
- References
- 18
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 1 · 2021: 1 · 2020: 5 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 4 · 2012: 1
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Wellcome Trust (068061)
- National Research Foundation
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Fondation de France
- University of California, San Diego
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- congenital lipoid adrenal hyperplasia, steroidogenic acute regulatory protein, STAR gene, frameshift mutation, missense mutations, 46,XY disorders of sex development, cholesterol side-chain cleavage, novel mutations
- MeSH terms
- Steroidogenic Acute Regulatory Protein, Adrenal Hyperplasia, Congenital, DNA Mutational Analysis, Female, Humans, Infant, Leucine, Pedigree, Phosphoproteins, Pregnenolone, Proline, Switzerland, Microsatellite Repeats, Mutation, Missense
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