Novel mutation in the gonadotropin-releasing hormone receptor (GNRHR) gene in a patient with normosmic isolated hypogonadotropic hypogonadism

We report a novel GNRHR mutation in a male with normosmic isolated hypogonadotropic hypogonadism (nIHH). The coding region of the GNRHR gene was amplified and sequenced. Three variants p.{[}Asn10Lys; Gln11Lys]; {[}Tyr283His] were identified in the GNRHR coding region in a male with sporadic complete nIHH. The three variants were absent in the controls (130 normal adults). Familial segregation showed that the previously described p. Asn10Lys and p. Gln11Lys are in the same allele, in compound heterozygozity with the novel variant p. Tyr283His. The p.{[}Asn10Lys; Gln11Lys] are known inactivating mutations. The p. Tyr283His affects a well-conserved residue, and in silico analysis suggested it is a deleterious variant. We describe a novel GNRHR mutation in a male with nIHH. Absence of the mutation in the control group, conservation among species, in silico analysis, and familial segregation suggest that p. Tyr283His, which was identified in compound heterozygozity with the p.{[}Asn10Lys; Gln11Lys] variants, is an inactivating mutation. Arq Bras Endocrinol Metab. 2012;56(8):540-4 (AU)