Molecular diagnosis of 46,XY DSD and identification of a novel 8 nucleotide deletion in exon 1 of the SRD5A2 gene

Journal of Pediatric Endocrinology and Metabolism

Volumn 23, Issue 4, 2010, Pages 379-385

  Nagaraja, M R ^a   Rastogi, Amit ^a   Raman, Rajiva ^b   Gupta, Dinesh K ^a   Singh, S K ^a,b  

^a BANARAS HINDU UNIVERSITY   (India)

^b BANARAS HINDU UNIVERSITY   (India)

Author keywords

46,XY DSD; Direct repeats; Hypomorphic mutation; Hypospadias; SRD5A2 gene

Indexed keywords

ANDROGEN; NUCLEOTIDE; STEROID 5ALPHA REDUCTASE 2; MEMBRANE PROTEIN; SRD5A2 PROTEIN, HUMAN; STEROID 5ALPHA REDUCTASE;

ADOLESCENT; ADULT; AMPLICON; ARTICLE; CHILD; CHROMOSOME DELETION; CLINICAL ARTICLE; DISORDER OF SEXUAL DEVELOPMENT; EXON; GENE DELETION; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC DISORDER; HUMAN; HYPOSPADIAS; KARYOTYPE 46,XY; MALE; MISSENSE MUTATION; MOLECULAR GENETICS; POLYMERASE CHAIN REACTION; PRESCHOOL CHILD; SCHOOL CHILD; SEXUAL DEVELOPMENT; GENETICS; GONADAL DYSGENESIS;

ADOLESCENT; ADULT; CHILD; CHILD, PRESCHOOL; EXONS; GONADAL DYSGENESIS, 46,XY; HUMANS; MALE; MEMBRANE PROTEINS; MUTATION, MISSENSE; NUCLEOTIDES; POLYMERASE CHAIN REACTION; SEQUENCE DELETION; TESTOSTERONE 5-ALPHA-REDUCTASE;

EID: 77954673776     PISSN: 0334018X     EISSN: None     Source Type: Journal    
DOI: 10.1515/jpem.2010.059     Document Type: Article

References (29)

1. Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS, Wilson EM. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 1988; 240: 327-330.
2. Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS. Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev 1995; 16: 271-321.
3. Andersson S, Russell DW. Structural and biochemical properties of cloned and expressed human and rat steroid 5α-reductases. Proc Natl Acad Sci U S A 1990; 87: 3640-3644. (Pubitemid 120015725)
4. Thigpen A, Davis DL, Milatovich A, Mendonca BB, Imperato-McGinley J, Griffin JE, Francke, U, Wilson JD, Russell DW. Molecular genetics of steroid 5α-reductase deficiency. J Clin Invest 1992; 90:799-809.
5. Wigley CW, Prihoda JS, Mowszowics I, Mendonca BB, New MI, Wilson JD, Russell DW. Natural mutagenesis study of the human steroid 5α-reductase 2 isozyme. Biochemistry 1994; 33:1265-1270.
6. Labrie F, Sugimoto Y, Luu-The V, Simard J, Lachance Y, Bachvarov D, Leblanc G, Durocher, F, Paquet N. Structure of human type II 5alpha-reductase gene. Endocrinology 1992; 131: 1571-1573.
7. Wilson JD, Griffin JE, Russell DW. Steriod 5α-Reductase 2 Deficiency. Endocr Rev 1993; 14: 577-593.
8. Imperato-McGinley J, Zhu YS. Androgens and male physiology the syndrome of 5alphareductase-2 deficiency. Mol Cell Endocrinol 2002; 198: 51-59.
9. Rusell DW, Wilson JD. Steroid 5α-Reductase: two genes/two enzymes. Annu Rev Biochem 1994; 63: 25-61.
10. Sinnecker GHG, Hiort O, Dibbelt L, Albers N, Dorr HG, Haub H, Heinrich U, Hemminghaus M, Hoepffher W, Holder M, Schnabel D, Krause K. Phenotypic classification of male pseudohermaphroditism due to Steriod 5α-Reductase 2 Deficiency. Am J Med Genet 1996; 63: 223-230.
11. Hackel C, Oliveira LE, Ferraz LF, Tonini MM, Silva, DN, Toralles MB, Stuchi-Perez EG, Guerra-Junior G. New mutations, hotspots, and founder effects in Brazilian patients with steroid 5alpha-reductase deficiency type 2. J Mol Med 2005; 83: 569-576.
12. Zhu YS, Cai LQ, Cordero JJ, Canovatchel WJ, Katz MD, Imperato-McGinley J. A novel mutation in the CAG triplet region of exon 1 of androgen receptor gene causes complete androgen insensitivity syndrome in a large kindred. J Clin Endocrinol Metab 1999; 84: 1590-1594.
13. Hiort O, Sinnecker GHG, Willenbring H, Lehners A, Zollner A, Struve D. Nonisotopic single strand conformation analysis of the 5α-Reductase type 2 gene for the diagnosis of 5α-Reductase 2 Deficiency. J Clin Endocrinol Metab 1996; 81: 3415-3418.
14. Nagaraja MR, Rastogi A, Raman R, Gupta DK, Singh SK. Mutational analysis of the androgen receptor gene in two Indian families with partial androgen insensitivity syndrome. J Pediatr Endocrinol Metab 2009; 22: 1169-1174.
15. Hiort O, Wodtke A, Struve D, Zollner A, Sinnecker GH. Detection of point mutations in the androgen receptor gene using non-isotopic single strand conformation polymorphism analysis. Hum Mol Genet 1994; 3: 1163-1166. (Pubitemid 24211964)
16. Thigpen A, Davis DL, Gautier T, Imperato-McGinley J, Russell DW. The molecular basis of steroid 5α-reductase deficiency in a large Dominian kindred. N Eng J Med 1992; 327: 1216-1219.
17. Vilchis F, Mendez JP, Canto P, Lieberman E, Chavez B. Identification of missense mutations in the SRD5A2 gene from patients with steroid 5alpha-reductase 2 deficiency. Clin Endocrinol 2000; 52: 383-387.
18. Wang Y, Li Q, Xu J, Liu Q, Wang W, Lin Y, Ma F, Chen T, Li S, Shen Y. Mutation analysis of five candidate genes in Chinese patients with hypospadias. Eur J Hum Genet 2004; 12: 706-712.
19. Nicoletti A, Baldazzi L, Balsamo A, Barp L, Pirazzoli P, Gennari M, Radetti G, Cacciariari E, Cicognani A. SRD5A2 gene analysis in an Italian population of undermasculinized 46,XY patients. Clin Endocrinol 2005; 63: 375-380.
20. Eunice M, Philibert P, Kulshreshtha B, Audran F, Paris F, Khurana ML, Pulikkanath PE, Kucheria K, Sultan C, Ammini AC. Molecular diagnosis of 5α-reductase 2 gene mutation in two Indian families with male pseudohermaphroditism. Asian J Androl 2008; 10: 815-818.
21. Sahu R, Boddula R, Sharma P, Bhatia V, Greaves R, Rao S, Desai M, Wakhlu A, Phadke S, Shukla M et al. Genetic Analysis of the SRD5A2 gene in Indian patients with 5αReductase Deficiency. J Pediatr Endocrinol Metab 2009; 22:247-254.
22. Makridakis N, Ross RK, Pike MC, Chang L, Stanczyk FZ, Kolonel LN, Shi CY, Yu MC, Henderson BE, Reichardt JK. A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase. Cancer Res 1997; 57: 1020-1022.
23. Krawczak M, Cooper DN. Gene deletions causing human genetic disease: mechanisms of mutagenesis and the role of the local DNA sequence environment. Hum Genet 1991; 86:425-441.
24. Carpenter TO, Imperato-McGinley J, Boulware SD, Weiss RM, Shackleton C, Griffin JE, Wilson JD. Variable expression of 5 alpha-reductase deficiency: presentation with male phenotype in a child of Greek origin. J Clin Endocrinol Metab 1990; 71: 318-322.
25. Can S, Zhu YS, Cai LQ, Ling Q, Katz MD, Akgun S, Shackleton CH, Imperato-McGinley J. The identification of 5alpha-reductase-2 and 17 beta-hydroxysteroid dehydrogenase-3 gene defects in male pseudohermaphrodites from a Turkish kindred. J Clin Endocrinol Metab 1998; 83: 560-569.
26. Nordenskjold A, Ivarsson SA. Molecular characterization of 5α-Reductase type 2 deficiency and fertility in a Swedish family. J Clin Endocrinol Metab 1998; 83: 3236-3238.
27. Baldinotti F, Majore S, Fogli A, Marrocco G, Ghirri P, Vuerich M, Tumini S, Boscherini B, Vetri M, Scommegna S, et al. Molecular characterization of 6 unrelated Italian patients with 5 α-Reductase type 2 deficiency. J Androl 2008; 29: 20-28.
28. Kulshreshtha B, Philibert P, Eunice M, Audran F, Paris F, Khurana ML, Ammini AC, Charles S. Phenotype, hormonal profile and genotype of patients with partial androgen insensitivity syndrome: report of a family with four adult males and one child with disorder of sexual diferentiation. Andrologia 2009; 41: 257-263.
29. Sasaki G, Ogata T, Ishii T, Kosaki K, Sato S, Homma K, Takahashi T, Hasegawa T, Matsuo N. Micropenis and the 5alpha-reductase-2 (SRD5A2) gene: Mutation and V89L polymorphism analysis in 81 Japanese patients. J Clin Endocrinol Metab 2003; 88: 3431-3436.