Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor

Article Article scientifique Rapport de cas Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor eng 1999 author Pralong François Pierre 24089 author Gomez François 37101 author Castillo Salgado Einar Eugenio 42985 author Cotecchia S author Abuin L author Aubert Michel 25310 author Portmann L author Gaillard Rolf Christian 22886 3811-3816 10.1210/jcem.84.10.6042 10523035 0021-972X In this study, we describe a patient with a phenotype of complete hypogonadotropic hypogonadism who presented primary failure of pulsatile GnRH therapy, but responded to exogenous gonadotropin administration. This patient bore a novel point mutation (T for A) at codon 168 of the gene encoding the GnRH receptor (GnRH-R), resulting in a serine to arginine change in the fourth transmembrane domain of the receptor. This novel mutation was present in the homozygous state in the patient, whereas it was in the heterozygous state in both phenotypically normal parents. When introduced into the complementary DNA coding for the GnRH-R, this mutation resulted in the complete loss of the receptor-mediated signaling response to GnRH. In conclusion, we report the first mutation of the GnRH-R gene that can induce a total loss of function of this receptor and is associated with a phenotype of complete hypogonadotropic hypogonadism. Adult Amino Acid Sequence/genetics Base Sequence/genetics Homozygote Humans Hypogonadism/genetics Male Point Mutation/genetics Receptors, LHRH/antagonists & inhibitors/genetics Dewey 616 Dewey 618 56 Département de médecine 221 58 Département de pédiatrie, gynécologie et obstétrique 223 false The Journal of clinical endocrinology and metabolism 84 10 35a5b474-423e-45a5-8c92-8d6f6542237e Article (Published version) Restricted 3811-3816.pdf 1264189 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

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Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor	The Journal of clinical endocrinology and metabolism			1999	542	0

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Gomez, François