A novel compound variant in GNRHR causing congenital idiopathic hypogonadotropic hypogonadism in a young male Korean patient

Abstract

Idiopathic hypogonadotropic hypogonadism (IHH) is a disease that shows symptoms of no or incomplete sexual maturation after 18 years old. The mutation of gonadotropin releasing hormone receptor gene (GNRHR) has been reported as the cause in 16% of total IHH patients. An 18-year-old adolescent was referred to endocrinology department for hypogonadism. He was born with cryptorchidism, had small testes at the age of 7 years, and showed low testosterone levels.Management of his hypogonadism was delayed due to his uncontrolled nephrotic syndrome. There were no abnormal findings on the brain MRI; atrophied testes discovered on his pelvis MRI; low levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were observed. In the HCG simulation test, testosterone levels showed no significant increase, rising from 1.11 to 1.15 ng/dL. The patient harbored a novel compound heterozygous variant of c.514G>A (p.Gly172Arg) and c.113G>A (p.Arg38Gln) in the GNRHR gene. Here, we report a case of new GNRHR compound variant c.514G>A (p.Gly172Arg) and c.113G>A (p.Arg38Gln) in a Korean adolescent for hypogonadotropic hypogonadism.

Causas poco frecuentes de amenorrea debida a hipogonadismo hipogonadotrópico

“…El gen GNRHR codifica para el receptor de GnRH, mutaciones en este receptor llevan a HH normósmico, al igual que algunos de los ya mencionados desórdenes hereditarios hipotalámicos. Las mutaciones en este receptor explican el 16% del total de los casos de HH idiopático (18). El GNRHR se expresa en las células gonadotropas de la hipófisis y pertenece a la familia de receptores acoplados a proteínas G del tipo A (19,20).…”