The first clinical presentation of disorders of sex development 46 XY due to mutation in Steroidogenic factor 1 (SF1) in Russian Literature
Natalia Yur'evna Kalinchenko,
Tatiana Aleksandrovna Anosova,
Vitaliy Alekseevich Ioutsi,
Anatoly Nikolaevich Tiulpakov https://doi.org/10.14341/probl201662155-59
Abstract
Steroidogenic factor 1 (SF1/AdBP4/FTZF1, NR5A1) is a nuclear receptor transcription factor that plays a critical role in different processes of sex development. Homozygous mutations in SF1 result in adrenal failure and complete testicular disgenesis in 46,XY individuals. According to recent studies heterozygous mutations in SF1 are associated with milder phenotype: they are found in children with 46,XY disorders of sex development (DSD) but with apparently normal adrenal structure and function. Here we present for the first time in Russian literature a case of SF1 deficiency. Molecular genetic analysis of NR5A1 gene revealed a novel heterozygous mutation c.951delC p.H317QfsX17. This clinical case demonstrates the importance of molecular genetic studies in DSD 46,XY, especially severe forms.
About the Authors
Natalia Yur'evna Kalinchenko
Endocrinology Research Centre
Russian Federation
MD, PhD
Competing Interests: нет
Russian Federation
MD, PhD
Competing Interests: нет
Tatiana Aleksandrovna Anosova
Moscow Pediatric clinic №125
Russian Federation
MD, PhD
Russian Federation
MD, PhD
Vitaliy Alekseevich Ioutsi
Endocrinology Research Centre
Russian Federation
MD, PhD
Russian Federation
MD, PhD
Anatoly Nikolaevich Tiulpakov
Endocrinology Research Centre
Russian Federation
MD, PhD
Russian Federation
MD, PhD
References
1. Achermann JC, Ito M, Ito M, et al. A Mutation In The Gene Encoding Steroidogenic Factor-1 Causes Xy Sex Reversal And Adrenal Failure In Humans. Nat Genet. 1999;22(2):125-126. doi: 10.1038/9629.
2. Kohler B, Lin L, Mazen I, et al. The Spectrum Of Phenotypes Associated With Mutations In Steroidogenic Factor 1 (Sf-1, Nr5a1, Ad4bp) Includes Severe Penoscrotal Hypospadias In 46,Xy Males Without Adrenal Insufficiency. Eur J Endocrinol. 2009;161(2):237-242. doi: 10.1530/Eje-09-0067.
3. Thomson SA, Baldwin WS, Wang YH, et al. Annotation, phylogenetics, and expression of the nuclear receptors in Daphnia pulex. BMC Genomics. 2009;10:500. doi: 10.1186/1471-2164-10-500.
4. Sadovsky Y, Crawford PA, Woodson KG, et al. Mice deficient in the orphan receptor steroidogenic factor 1 lack adrenal glands and gonads but express P450 side-chain-cleavage enzyme in the placenta and have normal embryonic serum levels of corticosteroids. Proc Natl Acad Sci USA. 1995;92(24):10939-10943. PMC40546.
5. Hasegawa T, Fukami M, Sato N, et al. Testicular dysgenesis without adrenal insufficiency in a 46,XY patient with a heterozygous inactive mutation of steroidogenic factor-1. J Clin Endocrinol Metab. 2004;89(12):5930-5935. doi: 10.1210/jc.2004-0935.
6. Kohler B, Lin L, Ferraz-de-Souza B, et al. Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency. Hum Mutat. 2008;29(1):59-64. doi: 10.1002/humu.20588.
7. Lin L, Achermann JC. Steroidogenic factor-1 (SF-1, Ad4BP, NR5A1) and disorders of testis development. Sex Dev. 2008;2(4-5):200-209. doi: 10.1159/000152036.
8. Rubtsov P, Nizhnik A, Dedov I, et al. Partial deficiency of 17alpha-hydroxylase/17,20-lyase caused by a novel missense mutation in the canonical cytochrome heme-interacting motif. Eur J Endocrinol. 2015;172(5):K19-25. doi: 10.1530/EJE-14-0834.
9. Dunnen JTd, Antonarakis SE. Mutation nomenclature extensions and suggestions to describe complex mutations: A discussion. Hum Mutat. 2000;15(1):7-12. doi: 10.1002/(sici)1098-1004(200001)15:1<7::aid-humu4>3.0.co;2-n.
10. Lourenco D, Brauner R, Lin L, et al. Mutations in NR5A1 associated with ovarian insufficiency. N Engl J Med. 2009;360(12): 1200-1210. doi: 10.1056/NEJMoa0806228.
11. Oba K, Yanase T, Nomura M, et al. Structural Characterization of HumanAd4bp (SF-1)Gene. Biochem Biophys Res Commun. 1996;226(1):261-267. doi: 10.1006/bbrc.1996.1343
12. Hammer GD, Krylova I, Zhang Y, et al. Phosphorylation of the Nuclear Receptor SF-1 Modulates Cofactor Recruitment. Mol Cell. 1999;3(4):521-526. doi: 10.1016/s1097-2765(00)80480-3.
13. Achermann JC, Ozisik G, Ito M, et al. Gonadal Determination and Adrenal Development Are Regulated by the Orphan Nuclear Receptor Steroidogenic Factor-1, in a Dose-Dependent Manner. J Clin Endocr Metab. 2002;87(4):1829-1833. doi: 10.1210/jcem.87.4.8376.
14. Biason-Lauber A, Schoenle EJ. Apparently normal ovarian differentiation in a prepubertal girl with transcriptionally inactive steroidogenic factor 1 (NR5A1/SF-1) and adrenocortical insufficiency. Am J Hum Genet. 2000;67(6):1563-1568. doi: 10.1086/316893.
15. Lin L, Philibert P, Ferraz-de-Souza B, et al. Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) are associated with 46,XY disorders of sex development with normal adrenal function. J Clin Endocrinol Metab.2007;92(3):991-999. doi: 10.1210/jc.2006-1672.
16. Correa RV, Domenice S, Bingham NC, et al. A microdeletion in the ligand binding domain of human steroidogenic factor 1 causes XY sex reversal without adrenal insufficiency. J Clin Endocrinol Metab. 2004;89(4):1767-1772. doi: 10.1210/jc.2003-031240.
Supplementary files
Review
For citations:
Kalinchenko N.Yu., Anosova T.A., Ioutsi V.A., Tiulpakov A.N. The first clinical presentation of disorders of sex development 46 XY due to mutation in Steroidogenic factor 1 (SF1) in Russian Literature. Problems of Endocrinology. 2016;62(1):55-59. https://doi.org/10.14341/probl201662155-59
Views:
660
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
.jpg){kind=logo}
