Clinical phenotype and infertility treatment in a male with hypogonadotropic hypogonadism due to mutations Ala129Asp/Arg262Gln of the gonadotropin-releasing hormone receptor.
OBJECTIVE
To characterize the genotype and phenotype of a man with idiopathic hypogonadism with infertility.


METHODS
Molecular analysis and clinical description.


METHODS
Medical school laboratory and reproductive endocrine clinic.A 40-year-old male with idiopathic hypogonadotropic hypogonadism.


METHODS
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.


METHODS
GNRHR mutation detection, genotype/phenotype correlation, and testicular response to exogenous gonadotropin therapy.


RESULTS
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.


CONCLUSIONS
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.
Layman
Lawrence C
LC
and Genetics, Department of Obstetrics and Gynecology, Neurobiology Program, The Institute of Molecular Medicine and Genetics, The Medical College of Georgia., Augusta, Georgia 30912-3360, USA. llayman@mail.mcg.edu
Cohen
David P
DP
Xie
Jun
J
Smith
Gary D
GD
D000328:Adult; D000409:Alanine; D001120:Arginine; D001224:Aspartic Acid; D006063:Chorionic Gonadotropin / Q000627:therapeutic use*; D005640:Follicle Stimulating Hormone / Q000627:therapeutic use*; D005838:Genotype; D005973:Glutamine; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D007006:Hypogonadism / Q000150:complications* / Q000235:genetics*; D007248:Infertility, Male / Q000188:drug therapy*; D008297:Male; D009154:Mutation / Q000235:genetics*; D009845:Oligospermia / Q000209:etiology; D010641:Phenotype; D011966:Receptors, LHRH / Q000235:genetics*
D006063:Chorionic Gonadotropin; D006728:Hormones; D011966:Receptors, LHRH; D005973:Glutamine; D001224:Aspartic Acid; D005640:Follicle Stimulating Hormone; D001120:Arginine; D000409:Alanine