Clinical phenotype and infertility treatment in a male with hypogonadotropic hypogonadism due to mutations Ala129Asp/Arg262Gln of the gonadotropin-releasing hormone receptor

• Published in: Fertility and sterility Vol. 78; no. 6; pp. 1317 - 1320
• Main Authors: Layman, Lawrence C, Cohen, David P, Xie, Jun, Smith, Gary D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2002; Elsevier Science
• Subjects: Adult; Alanine; Arginine; Aspartic Acid; Biological and medical sciences; Chorionic Gonadotropin - therapeutic use; Follicle Stimulating Hormone - therapeutic use; Genotype; Glutamine; Gynecology. Andrology. Obstetrics; Hormones - therapeutic use; Humans; Hypogonadism - complications; Hypogonadism - genetics; Infertility, Male - drug therapy; Male; Male genital diseases; Medical sciences; Mutation - genetics; Non tumoral diseases; Oligospermia - etiology; Phenotype; Receptors, LHRH - genetics; Endocrinopathy; Human; Hypogonadotropic hypogonadism; Hypothalamic diseases; Gonadotropin RH; Genotype; Genital diseases; Hypothalamic hormone; Case study; Phenotype; Mutation; Hormone releasing factor; Hormonal receptor
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/S0015-0282(02)04341-8

To characterize the genotype and phenotype of a man with idiopathic hypogonadism with infertility. Molecular analysis and clinical description. Medical school laboratory and reproductive endocrine clinic. A 40-year-old male with idiopathic hypogonadotropic hypogonadism. Denaturing gradient gel electrophoresis analysis and DNA sequencing of the gonadotropin-releasing hormone receptor (GNRHR) gene were performed. The patient was treated with hCG and FSH. GNRHR mutation detection, genotype/phenotype correlation, and testicular response to exogenous gonadotropin therapy. The proband demonstrated compound heterozygosity for Ala129Asp/Arg262Gln GNRHR mutations. He had a complete form of idiopathic hypogonadotropic hypogonadism, with descended testes and severe oligospermia but little response to exogenous gonadotropins. The phenotype of this patient differs from the one other family described with the same mutations. Exogenous gonadotropin therapy may not be as beneficial for increasing sperm concentration in older men with idiopathic hypogonadotropic hypogonadism.