Identification of a novel mutation in exon 1 of androgen receptor gene in an azoospermic patient with mild androgen insensitivity syndrome: case report and literature review

• Published in: Fertility and sterility Vol. 96; no. 5; pp. 1165 - 1169
• Main Authors: Goglia, Umberto, M.D., Ph.D, Vinanzi, Cinzia, Ph.D, Zuccarello, Daniela, M.D., Ph.D, Malpassi, Davide, M.D, Ameri, Pietro, M.D, Casu, Massimo, M.D, Minuto, Francesco, M.D, Foresta, Carlo, M.D, Ferone, Diego, M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2011; Elsevier
• Subjects: alanine; Amino Acid Sequence; androgen receptor; androgen receptors; Androgen-Insensitivity Syndrome - blood; Androgen-Insensitivity Syndrome - genetics; Androgen-Insensitivity Syndrome - physiopathology; azoospermia; Azoospermia - blood; Azoospermia - genetics; Azoospermia - physiopathology; Biological and medical sciences; Birth control; case studies; cryptorchidism; DNA Mutational Analysis; Exons; genes; Genetic Predisposition to Disease; gonadotropins; Gonadotropins - blood; Gynecology. Andrology. Obstetrics; Humans; Internal Medicine; Karyotyping; Male; Medical sciences; Middle Aged; mild androgen insensitivity syndrome; Molecular Sequence Data; mutation; Mutation, Missense; Novel mutation; Obstetrics and Gynecology; patients; Phenotype; Receptors, Androgen - genetics; serine; Sterility. Assisted procreation; Testosterone - blood; transcriptional activation; androgen receptor; azoospermia; mild androgen insensitivity syndrome; Novel mutation; Endocrinopathy; Human; Androgen; Pseudohermaphroditism; Gynecology; Sexual differentiation disorder; Identification; Review; Congenital disease; Obstetrics; Genital diseases; Case study; Target tissue resistance; Azoospermia; Exon; Gene; Male sterility; Mutation; Male genital diseases; Bibliographic review; Hormonal receptor
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2011.08.033

Objective To report a case of an azoospermic subject with mild androgen insensitivity syndrome (MAIS) and review the relevant literature. Design Case report. Setting Academic research hospital. Patient(s) A 49-year-old man with undermasculinized features and a history of cryptorchidism and azoospermia. Intervention(s) Hormonal evaluation and genetic testing of the androgen receptor gene ( AR ). Main Outcome Measure(s) Hormonal levels and sequence chromatogram of the proband and his mother. Result(s) We found total T in the normal range and high levels of gonadotropins. Karyotype was 46,XY. Genetic testing identified a novel mutation of exon 1 of AR , which resulted in an alanine to serine substitution in the transactivation domain at codon 240 (A240S). Fourteen other mutations of exon 1 of AR have been associated with MAIS to date. Conclusion(s) The novel mutation A240S of AR is involved in MAIS, a syndrome associated with azoospermia.