Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency

Human Mutation

Volumn 29, Issue 1, 2008, Pages 59-64

  Köhler, Birgit ^a,e   Lin, Lin ^b   Ferraz de Souza, Bruno ^b   Wieacker, Peter ^c   Heidemann, Peter ^d   Schröder, Vanessa ^a   Biebermann, Heike ^a   Schnabel, Dirk ^a   Grüters, Annette ^a   Achermann, John C ^b  

^a HUMBOLDT UNIVERSITY   (Germany)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c OTTO VON GUERICKE UNIVERSITY   (Germany)

^d Children's Hospital   (Germany)

^e CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Disorders of sex development (DSD); Gonadal dysgenesis; Male pseudohermaphroditism; NR5A1; Nuclear receptor; SF1; Steroidogenic factor 1

Indexed keywords

STEROIDOGENIC FACTOR 1;

ADOLESCENT; ADRENAL FUNCTION; ADRENAL INSUFFICIENCY; ADULT; ARTICLE; CLINICAL ARTICLE; DNA BINDING; FEMALE; FRAMESHIFT MUTATION; GENE CONTROL; GENE MUTATION; GENETIC ANALYSIS; GONAD DEVELOPMENT; GONADAL DYSGENESIS; HUMAN; MALE PSEUDOHERMAPHRODITISM; MISSENSE MUTATION; NONSENSE MUTATION; NUCLEOTIDE SEQUENCE; PRESCHOOL CHILD; PRIORITY JOURNAL; PROTEIN FUNCTION; RNA STABILITY; SCHOOL CHILD; SEXUAL DEVELOPMENT; STEROIDOGENESIS; TRANSCRIPTION INITIATION;

ADOLESCENT; ADRENAL GLANDS; ADRENAL INSUFFICIENCY; ADULT; CHILD; CHILD, PRESCHOOL; COHORT STUDIES; FEMALE; GONADAL DYSGENESIS, 46,XY; HUMANS; MUTATION; STEROIDOGENIC FACTOR 1;

EID: 38149046500     PISSN: 10597794     EISSN: None     Source Type: Journal    
DOI: 10.1002/humu.20588     Document Type: Article

References (26)

1. Achermann JC, Ito M, Ito M, Hindmarsh PC, Jameson JL. 1999. A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. Nat Genet 22:125-126.
2. Achermann JC, Ozisik G, Ito M, Orun UA, Harmanci K, Gurakan B, Jameson JL. 2002. Gonadal determination and adrenal development are regulated by the orphan nuclear receptor steroidogenic factor-1, in a dose-dependent manner. J Clin Endocrinol Metah 87:1829-1833.
3. Baumann CT, Ma H, Wolford R, Reyes JC, Maruvada P, Lim C, Yen PM, Stallcup MR, Hager GL. 2001. The glucocorticoid receptor interacting protein 1 (GRIP1) localizes in discrete nuclear foci that associate with ND10 bodies and are enriched in components of the 26S proteasome. Mol Endocrinol 15:485-500.
4. Biason-Lauber A, Schoenle EJ. 2000. Apparently normal ovarian differentiation in a prepubertal girl with transcriptionally inactive steroidogenic factor 1 (NR5A1/SF-1) and adrenocortical insufficiency. Am J Hum Genet 67:1563-1568.
5. Black BE, Vitto MJ, Gioeli D, Spencer A, Afshar N, Conaway MR, Weher MJ, Paschal BM. 2004. Transient, ligand-dependent arrest of the androgen receptor in subnuclear foci alters phosphorylation and coactivator interactions. Mol Endocrinol 18:834-850.
6. Bland ML, Jamieson CA, Akana SF, Bornstein SR, Eisenhofer G, Dallman MF, Ingraham HA. 2000. Haploinsufficiency of steroidogenic factor-1 in mice disrupts adrenal development leading to an impaired stress response. Proc Natl Acad Sci USA 97:14488-14493.
7. Correa RV, Domenice S, Bingham NC, Billerbeck AE, Rainey WE, Parker KL, Mendonca BB. 2004. A microdeletion in the ligand binding domain of human steroidogenic factor 1 causes XY sex reversal without adrenal insufficiency. J Clin Endocrinol Metab 89:1767-1772.
8. Hanley NA, Ball SG, Clement-Jones M, Hagan DM, Strachan T, Lindsay S, Robson S, Ostrer H, Parker KL, Wilson DI. 1999. Expression of steroidogenic factor 1 and Wilms' tumour 1 during early human gonadal development and sex determination. Mech Dev 87:175-180.
9. Hasegawa T, Fukami M, Sato N, Katsumata N, Sasaki G, Fukutani K, Morohashi K, Ogata T. 2004. Testicular dysgenesis without adrenal insufficiency in a 46,XY patient with a heterozygous inactive mutation of steroidogenic factor-1. J Clin Endocrinol Metab 89:5930-5931.
10. Hatano O, Takayama K, Imai T, Waterman MR, Takakusu A, Omura T, Morohashi KR. 1994. Sex-dependent expression of a transcription factor, Ad4BP, regulating steroidogenic P-450 genes in the gonads during prenatal and postnatal rat development. Development 120:2787-2797.
11. Ingraham HA, Lala DS, Ikeda Y, Luo X, Shen WH, Nachtigal MW, Ahbud R, Nilson JH, Parker KL. 1994. The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis. Genes Dev 8:2302-2312.
12. Ito M, Achermann JC, Jameson JL. 2000. A naturally occurring steroidogenic factor-1 mutation exhibits differential binding and activation of target genes. J Biol Chem 275:31708-31714.
13. Jameson JL. 2004. Of mice and men: the tale of steroidogenic factor-1. J Clin Endocrinol Metab 89:5927-5929.
14. Krylova IN, Sablin EP, Moore J, Xu RX, Waitt GM, MacKay JA, Juzumiene D, Bynum JM, Madauss K, Montana V, Bebedeva L, Suzawz M, Williams JD, Williams SP, Guy RK, Thornton JW, Fletterick RJ, Willson TM, Ingraham HA. 2005. Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1. Cell 120:343-355.
15. Lala DS, Rice DA, Parker KL. 1992. Steroidogenic factor I, a key regulator of steroidogenic enzyme expression, is the mouse homolog of fushi tarazu-factor I. Mol Endocrinol 6:1249-2458.
16. Lin L, Gu WX, Ozisik G, To WS, Owen CJ, Jameson JL, Achermann JC. 2006. Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (SF1/Ad4BP, NR5A1) in children and adults with primary adrenal failure: ten years' experience. J Clin Endocrinol Metab 91:3048-3054.
17. Lin L, Philibert P, Ferraz-de-Souza B, Kelberman D, Homfray T, Albanese A, Molini V, Sebire NJ, Einaudi S, Conway GS, Hughes IA, Jameson JL, Sultan C, Dattani MT, Achermann JC. 2007. 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 92:991-999.
18. Luo X, Ikeda Y, Parker KL. 1994. A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 77:481-490.
19. Majdic G, Young M, Gomez-Sanchez E, Anderson P, Szczepaniak LS, Dobbins RL, McGarry JD, Parker KL. 2002. Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity. Endocrinology 143:607-614.
20. Mallet D, Bretones P, Michel-Calemard L, Dijoud F, David M, Morel Y. 2004. Gonadal dysgenesis without adrenal insufficiency in a 46, XY patient heterozygous for the nonsense C16X mutation: a case of SF1 haploinsufficiency. J Clin Endocrinol Metab 89:4829-4832.
21. Parker KL, Schimmer BP. 1997. Steroidogenic factor 1: a key determinant of endocrine development and function. Endocr Rev 18:361-377.
22. Parker KL, Rice DA, Lala DS, Ikeda Y, Luo X, Wong M, Bakke M, Zhao L, Frigeri C, Hanley NA, Stallings N, Schimmer BP. 2002. Steroidogenic factor 1: an essential mediator of endocrine development. Recent Prog Horm Res 57:19-36.
23. Vottero A, Kino T, Combe H, Lecomte P, Chrousos GP 2002. A novel, C-terminal dominant negative mutation of the GR causes familial glucocorticoid resistance through abnormal interactions with p160 steroid receptor coactivators. J Clin Endocrinol Metab 87:2658-2667.
24. Wada Y, Okada M, Hasegawa T, Ogata T. 2005. Association of severe micropenis with Gly146Ala polymorphism in the gene for steroidogenic factor-1. Endocr J 52:445-448.
25. Wada Y, Okada M, Fukami M, Sasagawa I, Ogata T. 2006. Association of cryptorchidism with Gly146Ala polymorphism in the gene for steroidogenic factor-1. Fertil Steril 85:787-790.
26. WuQiang F, Yanase T, Wei L, Oba K, Nomura M, Okabe T, Goto K, Nawata H. 2003. Functional characterization of a new human Ad4BP/SF-1 variation, G146A. Biochem Biophys Res Commun 311:987-994.