A novel point mutation in the hormone binding domain of the androgen receptor associated with partial and minimal androgen insensitivity syndrome

Journal of Pediatric Endocrinology and Metabolism

Volumn 16, Issue 2, 2003, Pages 149-154

  Galli Tsinopoulou, Assimina ^a,b   Hiort, Olaf ^c   Schuster, Tobias ^a   Messer, Gerald ^d   Kuhnle, Ursula ^a,d  

^a UNIVERSITY OF MUNICH   (Germany)

^b ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^c UNIVERSITY OF LÜBECK   (Germany)

^d LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

Author keywords

Androgen insensitivity syndrome; Phenotypic variability

Indexed keywords

ANDROGEN RECEPTOR; GONADOTROPIN; ISOLEUCINE; TESTOSTERONE; THREONINE; ANDROGEN; LUTEINIZING HORMONE;

ADULT; ANDROGEN INSENSITIVITY SYNDROME; ARTICLE; CLINICAL ARTICLE; CLINICAL FEATURE; CODON; CRYPTORCHISM; EXON; FAMILY HISTORY; GENE SEQUENCE; GENETIC CODE; GENETIC VARIABILITY; GYNECOMASTIA; HORMONE BINDING; HUMAN; HYPOSPADIAS; INFANT; KARYOTYPE 46,XY; MALE; MALE GENITAL TRACT MALFORMATION; OLIGOSPERMIA; PHENOTYPE; POINT MUTATION; SEMEN ANALYSIS; SEX DIFFERENTIATION; SEXUAL ORIENTATION; BLOOD; CASE REPORT; GENETICS; METABOLISM; PEDIGREE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ADULT; ANDROGEN-INSENSITIVITY SYNDROME; ANDROGENS; CRYPTORCHIDISM; HUMANS; INFANT; LUTEINIZING HORMONE; MALE; PEDIGREE; POINT MUTATION; RECEPTORS, ANDROGEN; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; TESTOSTERONE;

EID: 0041413051     PISSN: 0334018X     EISSN: None     Source Type: Journal    
DOI: 10.1515/JPEM.2003.16.2.149     Document Type: Article

References (32)

1. Gottlieb B, Pinsky L, Beitel LK, Trifiro M. Androgen insensitivity. Am J Med Genet 1999; 89: 210-217.
2. McPhaul MJ, Marcelli M, Zoppi S, Griffin JE, Wilson JD. Genetic basis of endocrine disease. IV. The spectrum of mutations in the androgen receptor gene that causes androgen resistance. J Clin Endocrinol Metab 1993; 76: 17-23.
3. Gottlieb B, Beitel LK, Lumbroso R, Pinsky L, Trifiro M. Update of the androgen receptor gene mutations database. Hum Mut 1999; 14: 103-114.
4. 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.
5. Aiman J, Griffin JE, Gazak JM, Wilson JD, MacDonald PC. Androgen insensitivity as a cause of infertility in otherwise normal men. N Engl J Med 1979; 300: 223-227.
6. Hiort O, Huang Q, Sinnecker GHG, Sadeghi-Nejad A, Kruse K, Wolfe HJ, Yandell DW. Single strand conformation polymorphism (SSCP) analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes: application for diagnosis, genetic counseling, and therapy. J Clin Endocrinol Metab 1993; 77: 262-266.
7. Schmitt S, Knorr D, Schwarz HP, Kuhnle U. Gonadotropin regulation during puberty in complete androgen insensitivity syndrome with testicles in situ. Horm Res 1994; 42: 253-256.
8. De Bellis A, Quigley CA, Marschke KB, El-Awady MK, Lane MV, Smith EP, Sar M, Wilson EM, French FS. Characterization of mutant androgen receptors causing partial androgen insensitivity syndrome. J Clin Endocrinol Metab 1994; 78: 513-522.
9. Keenan BS, McNeel RL, Gonzales ET. Abnormality of intracellular 5α-dihydrotestosterone binding in simple hypospadias: studies on equilibrium binding in sonicates of genital skin fibroblasts. Pediatr Res 1984; 18: 216-220.
10. Batch JA, Evans BA, Hughes IA, Patterson MN. Mutations of the androgen receptor gene identified in perineal hypospadias. J Med Genet 1993; 30: 198-201.
11. Aiman J, Griffin JE. The frequency of androgen receptor deficiency in infertile men. J Clin Endocrinol Metab 1982; 54: 725-732.
12. Morrow AF, Gyorki S, Warne GL, Burger HG, Bangah ML, Outch KH, Mirovics A, Baker HWG. Variable androgen receptor levels in infertile men. J Clin Endocrinol Metab 1987; 64: 1115-1121.
13. Hiort O, Holterhus PM, Horter T, Schulze W, Kremke B, Bals-Pratsch M, Sinnecker G, Kruse K. Significance of mutations in the androgen receptor gene in males with idiopathic infertility. J Clin Endocrinol Metab 2000; 85: 2810-2815.
14. Sinnecker GHG, Hiort O, Nitsche EM, Holterhus PM, Kruse K. Functional assessment and clinical classification of androgen insensitivity in patients with mutations of the androgen receptor gene. German Collaborative Intersex Study Group. Eur J Pediatr 1997; 156: 7-14.
15. Pinsky L, Kaufman M, Killinger DW, Burko B, Shatz D, Volpe R. Human minimal androgen insensitivity with normal dihydrotestosterone-binding capacity in cultured genital skin fibroblasts: evidence for an androgen-selective qualitative abnormality of the receptor. Am J Hum Genet 1984; 36: 965-978.
16. Grino PB, Griffin JE, Cushard WG Jr, Wilson JD. A mutation of the androgen receptor associated with partial androgen resistance, familial gynecomastia and fertility. J Clin Endocrinol Metab 1984; 66: 754-761.
17. Brown TR, Maes M, Rothwell SW, Migeon CJ. Human complete androgen insensitivity with normal dihydrotestosterone receptor binding capacity in cultured genital fibroblasts: evidence for a qualitative abnormality of the receptor. J Clin Endocrinol Metab 1982; 55: 61-69.
18. Wilson JD, Harrod MJ, Goldstein JL, Hemsell DL, MacDonald PC. Familial incomplete male pseudohermaphroditism, type 1. Evidence for androgen resistance and variable clinical manifestations in a family with Reifenstein syndrome. N Engl J Med 1974; 290: 1097-1103.
19. Batch JA, Davies HR, Evans BAJ, Hughes IA, Patterson MN. Phenotypic variation and detection of carrier status in the partial androgen insensitivity syndrome. Arch Dis Child 1993; 68: 453-457.
20. Rodien P, Mebarki F, Mowszowicz I, Chaussain JL, Young J, Morel Y, Schaison G. Different phenotypes in a family with androgen insensitivity caused by the same M7801 point mutation in the androgen receptor gene. J Clin Endocrinol Metab 1996; 81: 2994-2998.
21. Tsukada T, Inoue M, Tachibana S, Nakai Y, Takebe H. An androgen receptor mutation causing androgen resistance in undervirilized male syndrome. J Clin Endocrinol Metab 1994; 79: 1202-1207.
22. Dowsing AT, Yong EL, Clark M, McLachlan RI, de Kretser DM, Trounson AO. Linkage between male infertility and trinucleotide repeat expansion in the androgen-receptor gene. Lancet 1999; 354: 640-643.
23. Hiort O, Horter T, Schulze W, Kremke B, Sinnecker GH. Male infertility and increased risk of diseases in future generations. Lancet 1999; 354: 1907-1908.
24. World Health Organization. WHO Laboratory Manual for the Examination of Human Semen, and Sperm-Cervical Mucus Interaction. Cambridge: Cambridge University Press, 1992.
25. Giwercman A, Kledal T, Schwartz M, Giwercman YL, Leffers H, Zazzi H, Wedell A, Skakkebaek NE. Preserved male fertility despite decreased androgen sensitivity caused by a mutation in the ligand-binding domain of the androgen receptor gene. J Clin Endocrinol Metab 2000; 85: 2253-2259.
26. Jenster G, van der Korput HAGM, van Vroonhoven C, van der Kwast TH, Trapman J, Brinkmann AO. Domains of the human androgen receptor involved in steroid binding, transcriptional activation, and subcellular localization. Mol Endocrinol 1991; 5: 1396-1404.
27. Brinkmann AO, Block LJ, de Rutier PE. Mechanisms of androgen receptor activation and function. J Steroid Biochem Mol Biol 1999; 69: 307-313.
28. Holterhus PM, Sinnecker GH, Hiort O. Phenotypic diversity and testosterone-induced normalization of mutant L712F androgen receptor function in a kindred with androgen insensitivity. J Clin Endocrinol Metab 2000; 85: 3245-3250.
29. Marcelli M, Zoppi S, Wilson CM, Griffin JE, McPhaul MJ. Amino acid substitutions in the hormone-binding domain of the human androgen receptor alter the stability of the hormone receptor complex. J Clin Invest 1994; 94: 1642-1650.
30. Evans BAJ, Hughes IA, Bevan CL, Patterson MN, Gregory JW. Phenotypic diversity in siblings with partial androgen insensitivity syndrome. Arch Dis Child 1997; 76: 529-531.
31. McPhaul MJ, Marcelli M, Tilley WD, Griffin JE, Wilson JD. Androgen resistance caused by mutations in the androgen receptor gene. FASEB J 1991; 5: 2910-2915.
32. Dipple KM, McCabe RB. Phenotypes of patients with "simple" Mendelian disorders are complex traits: thresholds, modifiers, and systems dynamics. Am J Hum Genet 2000; 66: 1729-1735.