Genetic and molecular aspects of hypospadias

European Journal of Pediatric Surgery

Volumn 14, Issue 5, 2004, Pages 297-302

  Utsch, B ^a,c   Albers, N ^b   Ludwig, M ^a  

^a UNIVERSITY OF BONN   (Germany)

^b Kinderhospital Osnabruck   (Germany)

^c UNIVERSITY HOSPITAL ERLANGEN   (Germany)

Author keywords

Aetiology; Candidate gene approaches; Genes; Hypospadias

Indexed keywords

CORTICOSTEROID; TESTOSTERONE;

ADRENAL GLAND; BIRTH; BLOOD SAMPLING; CHROMOSOME ABERRATION; CRYPTORCHISM; DNA MICROARRAY; DOMINANT INHERITANCE; GENE IDENTIFICATION; GENE LOCUS; HEREDITY; HERMAPHRODITISM; HUMAN; HYPOSPADIAS; MICROCEPHALY; NONHUMAN; PHENOTYPE; PROTEIN EXPRESSION; PROTEOMICS; REVIEW; SCROTUM DISORDER; SEX ROLE; STEROIDOGENESIS; TESTOSTERONE SYNTHESIS;

ABNORMALITIES, MULTIPLE; GENETIC RESEARCH; HUMANS; HYPOSPADIAS; MALE; SEX DIFFERENTIATION; STEROID METABOLISM, INBORN ERRORS; SYNDROME; URETHRA;

EID: 9344246273     PISSN: 09397248     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2004-821275     Document Type: Review

References (46)

1. Aaronson IA, Cakmak MA, Key LL. Defects of the testosterone biosynthetic pathway in boys with hypospadias. J Urol 1997; 157: 1884-1888
2. Abusheikha N, Lass A, Brinsden P. XX males without SRY gene and with infertility. Hum Reprod 2001; 16: 717-718
3. Albers N, Ulrichs C, Glüer S, Hiort O, Sinnecker GH, Mildenberger H et al. Etiologic classification of severe hypospadias: implications for prognosis and management. J. Pediatr 1997; 131: 386-392
4. Arpino C, Brescianini S, Robert E, Castilla EE, Cocchi G, Cornel MC, de Vigan C, Lancester PA, Merlob P, Sumiyoshi Y, Zampino G, Renzi C, Rosano A, Mastroiacovo P. Teratogenic effects of antiepileptic drugs: use of an international database on malformations and drug exposure (MADRE). Epilepsia 2000; 41: 1436-1443
5. Avellán L. The incidence of hypospadias in Sweden. Scand J Plast Reconstr Surg 1975; 9: 129-139
6. Baskin LS. Hypospadias and urethral development. J Urol 2000; 163: 951-956
7. Bauer SB, Retik AB, Colodny AH. Genetic aspects of hypospadias. Urol Clin North Am 1981; 8: 559-564
8. Benirschke K, Naftolin F, Gittes R, Khudr G, Yen SS, Allen Jr FH. True hermaphroditism and chimerism. Am J Obst Gynecol 1972; 113: 449-458
9. Cameron FJ, Sinclair AH. Mutations in SRY and SOX9: testis-determining genes. Hum Mutat 1997; 9: 388-395
10. Ericson A, Kallen B. Congenital malformations in infants born after IVF: a population-based study. Hum Reprod 2001; 16: 504-509
11. Federman DD, Donahoe PK. Ambiguous genitalia-etiology, diagnosis, and therapy. Adv Endocrinol Metab 1995; 6: 91-116
12. Geley S, Kapelari K, Jöhrer K, Peter M, Glatzl J, Vierhapper H, Schwarz S, Helmberg A, Sippell WG, White PC, Kofler R. CYP11B1 mutations causing congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. J Clin Endocrinol Metab 1996; 81: 2896-2901
13. Gibbons RJ, Ricketts DJ, Villard L, Higgs DR. Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome). Cell 1995; 80: 837-845
14. Gray Jr LE, Kelce WR. Latent effects of pesticides and toxic substances on sexual differentiation in rodents. Toxicol Ind Health 1996; 12: 515-531
15. Hiort O, Klauber G, Cendron M, Sinnecker GHG, Keim L, Schwinger E, Wolfe HJ, Yandell DW. Molecular characterization of the androgen receptor gene in boys with hypospadias. Eur J Pediatr 1994; 153: 317-321
16. Hiort O, Holterhus PM. The molecular basis of male sexual differentiation. Eur J Endocrinol 2000; 142: 101-110
17. Hiort O. Neonatal endocrinology of abnormal male sexual differentiation: molecular aspects. Hormon Res 2000; 53: 38-41
18. Holterhus PM, Hiort O, Demeter J, Brown PO, Brooks JD. Differential gene-expression patterns in genital fibroblasts of normal males and 46,XY females with androgen insensitivity syndrome: evidence for early programming involving the androgen receptor. Genome Biol 2003; 4: R37
19. Huang B, Wang S, Ning Y, Lamb AN, Bartley J. Autosomal XX sex reversal caused by duplication of SOX9. Am J Med Genet 1999; 87: 349-353
20. Imbeaud S, Faure E, Lamarre I, Mattei MG, di Clemente N, Tizard R, Carre-Eusebe D, Belville C, Tragethon L, Tonkin C et al. Insensitivity to anti-Mullerian hormone due to a mutation in the human anti-Mullerian hormone receptor. Nat Genet 1995; 11: 382-388
21. Joffe M. Are problems with male reproductive health caused by endocrine disruption? Occup Environ Med 2001; 58: 281-287
22. Kelce WR, Wilson EM. Environmental antiandrogens: developmental effects, molecular mechanisms, and clinical implications. J Mol Med 1997; 75: 198-207
23. Köhler B, Schumacher V, L'Allemand D, Royer-Pokora B, Gruters A. Germline Wilms' tumor suppressor gene (WT1) mutation leading to isolated genital malformation without Wilms' tumor or nephropathy. J Pediatr 2001; 138: 421-424
24. Martens JW, Verhoef-Post M, Abelin N, Ezabella M, Toledo SP, Brunner HG, Themmen AP. A homozygous mutation in the luteinizing hormone receptor causes partial Leydig cell hypoplasia: correlation between receptor activity and phenotype. Mol Endocrinol 1998; 12: 775-784
25. Mendonca BB, Inacio M, Arnhold IJ, Costa EM, Bloise W, Martin RM, Denes FT, Silva FA, Andersson S, Lindqvist A, Wilson JD. Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase 3 deficiency. Diagnosis, psychological evaluation, and management. Medicine (Baltimore) 2000; 79: 299-309
26. Misrahi M, Meduri G, Pissard S, Bouvattier C, Beau I, Loosfelt H, Jolivet A, Rappaport R, Milgrom E, Bougneres P. Comparison of immunocytochemical and molecular features with the phenotype in a case of incomplete male pseudohermaphroditism associated with a mutation of the luteinizing hormone receptor. J Clin Endocrinol Metab 1997; 82: 2159-2165
27. Moisan AM, Ricketts ML, Tardy V, Desrochers M, Mébarki F, Chaussain JL, Cabrol S, Raux-Demay MC, Forest MG, Sippell WG, Peter M, Morel Y, Simard J. New insight into the molecular basis of 3β-hydroxysteroid dehydrogenase deficiency: identification of eight mutations in the HSD3B2 gene in eleven patients from seven new families and comparison of the functional properties of twenty-five mutant enzymes. J Clin Endocrinol Metab 1999; 84: 4410-4425
28. Mortlock DP, Innis JW. Mutation of HOXA13 in hand-foot-genital syndrome. Nat Genet 1997; 15: 179-180
29. North K, Golding J. A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC study team. Avon longitudinal study of pregnancy and childhood. BJU Int 2000; 85: 107-113
30. Ottolenghi C, McElreavey K. Deletions of 9 p and the quest for a conserved mechanism of sex determination. Mol Genet Metab 2000; 71: 397-404
31. Palermo GD, Neri QV, Hariprashad JJ, Davis OK, Veeck LL, Rosen Z. ICSI and its outcome. Semin Reprod Med 2000; 18: 161-169
32. Raman-Wilms L, Tseng AL, Wighardt S, Einarson TR, Koren G. Fetal genital effects of first-trimester sex hormone exposure; meta-analysis. Obstet Gynecol 1995; 85: 141-149
33. Sheldon CA, Duckett JW. Hypospadias. Pediatr Clin North Am 1987; 34: 1259-1272
34. Silver RI, Russell DW. 5α-reductase type 2 mutations are present in some boys with isolated hypospadias. J Urol 1999; 162: 1142-1145
35. Speiser PW. Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Endocrinol Metab Clin North Am 2001; 30: 31-59
36. Sutherland RW, Wiener JS, Hicks JP, Marcelli M, Gonzales Jr ET, Roth DR, Lamb DJ. Androgen receptor gene mutations are rarely associated with isolated penile hypospadias. J Urol 1996; 156: 828-831
37. Toppari J, Skakkebaek NE. Sexual differentiation and environmental endocrine disrupters. Baillieres Clin Endocrinol Metab 1998; 12: 143-156
38. Utsch B, Albers N, Dame C, Bartmann P, Lentze MJ, Ludwig M. Homozygous alpha-thalassemia associated with hypospadias: SEA-type deletion does not affect expression of the -14 gene and loss of the thetal-globin gene on 16p13.3 is compensated by its duplicate theta2 on chromosome 10. Am J Med Genet 2001; 101: 286-287
39. Utsch B, Becker K, Brock D, Lentze MJ, Bidlingmaier F, Ludwig M. A novel stable polyalanine [poly(A)] expansion in the HOXA13 gene associated with hand-foot-genital syndrome: proper function of poly(A)-harbouring transcription factors depends on a critical repeat length? Hum Genet 2002; 110: 488-494
40. Utsch B, Kaya A, Özburun A, Lentze M, Albers N, Ludwig M. Exclusion of WTAP and HOXA13 as candidate genes for isolated hypospadias. Scand J Urol Nephrol 2003; 37: 498-501
41. Wagner T, Wirth J, Meyer J, Zabel B, Held M, Zimmer J, Pasantes J, Bricarelli FD, Keutel J, Hustert E et al. Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell 1994; 79: 1111-1120
42. Weidner IS, Møller H, Jensen TK, Skakkebik NE. Risk factors for cryptorchidism and hypospadias. J Urol 1999; 161: 1606-1609
43. Wennerholm UB, Bergh C, Hamberger L, Lundin K, Nilsson L, Wikland M, Kallen B. Incidence of congenital malformations in children born after ICSI. Hum Reprod 2000; 15: 944-948
44. Wilson JD, Griffin JE, Russell DW. Steroid 5 alpha-reductase 2 deficiency. Endocr Rev 1993; 14: 577-593
45. Yordam N, Alikasifoglu A, Kandemir N, Caglar M, Balci S. True hermaphroditism: clinical features, genetic variants and gonadal histology. J Pediatr Endocrinol Metab 2001; 14: 421-427
46. Zhang L, Mason JI, Naiki Y, Copeland KC, Castro-Magana M, Gordon-Walker TT, Chang YT, Pang S. Characterization of two novel homozygous missense mutations involving codon 6 and 259 of type II 3β-hydroxysteroid dehydrogenase (3betaHSD) gene causing, respectively, nonsalt-wasting and salt-wasting 3betaHSD deficiency disorder. J Clin Endocrinol Metab 2000; 85: 1678-1685