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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
R31C GNRH1 Mutation and Congenital Hypogonadotropic Hypogonadism
PLoS ONE, Volume 8, No. 7, Article e69616, Year 2013
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Description
Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare reproductive disease leading to lack of puberty and infertility. Loss-of-function mutations of GNRH1 gene are a very rare cause of autosomal recessive nCHH. R31C GNRH1 is the only missense mutation that affects the conserved GnRH decapeptide sequence. This mutation was identified in a CpG islet in nine nCHH subjects from four unrelated families, giving evidence for a putative "hot spot". Interestingly, all the nCHH patients carry this mutation in heterozygosis that strikingly contrasts with the recessive inheritance associated with frame shift and non-sense mutations. Therefore, after exclusion of a second genetic event, a comprehensive functional characterization of the mutant R31C GnRH was undertaken. Using different cellular models, we clearly demonstrate a dramatic reduction of the mutant decapeptide capacity to bind GnRH-receptor, to activate MAPK pathway and to trigger inositol phosphate accumulation and intracellular calcium mobilization. In addition it is less able than wild type to induce lh-beta transcription and LH secretion in gonadotrope cells. Finally, the absence of a negative dominance in vitro offers a unique opportunity to discuss the complex in vivo patho-physiology of this form of nCHH. © 2013 Maione et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3723855/bin/pone.0069616.s001.ppt
https://efashare.b-cdn.net/share/pmc/articles/PMC3723855/bin/pone.0069616.s002.ppt
https://efashare.b-cdn.net/share/pmc/articles/PMC3723855/bin/pone.0069616.s003.ppt
https://efashare.b-cdn.net/share/pmc/articles/PMC3723855/bin/pone.0069616.s004.doc
Authors & Co-Authors
Maione, L.
France, Gif-sur-yvette
Université Paris-saclay
France, Le Kremlin-bicetre
Hopital de Bicetre
Italy, Naples
Università Degli Studi Di Napoli Federico Ii
Albarel, F.
France, Marseille
Hopital la Timone
Bouchard, Philippe
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Gallant, Megan
South Africa, Cape Town
Faculty of Health Sciences
Flanagan, Colleen A.
South Africa, Cape Town
Faculty of Health Sciences
South Africa, Johannesburg
University of the Witwatersrand Faculty of Health Sciences
Bobe, Regis
France, Gif-sur-yvette
Université Paris-saclay
Cohen-Tannoudji, Joelle
France, Paris
Unité de Biologie Fonctionnelle et Adaptative Bfa
Pivonello, Rosario
Italy, Naples
Università Degli Studi Di Napoli Federico Ii
Colao, Annamaria
Italy, Naples
Università Degli Studi Di Napoli Federico Ii
Brue, Thierry C.
France, Marseille
Hopital la Timone
Millar, Robert P.
South Africa, Cape Town
Faculty of Health Sciences
South Africa, Pretoria
University of Pretoria
United Kingdom, Edinburgh
University of Edinburgh, College of Medicine and Veterinary Medicine
Lombés, Marc
France, Gif-sur-yvette
Université Paris-saclay
Young, Jacques M.
France, Gif-sur-yvette
Université Paris-saclay
France, Le Kremlin-bicetre
Hopital de Bicetre
Guiochon-Mantel, Anne
France, Gif-sur-yvette
Université Paris-saclay
France, Le Kremlin-bicetre
Hopital de Bicetre
Bouligand, Jérôme
France, Gif-sur-yvette
Université Paris-saclay
France, Le Kremlin-bicetre
Hopital de Bicetre
Statistics
Citations: 18
Authors: 15
Affiliations: 10
Identifiers
Doi:
10.1371/journal.pone.0069616
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics
Sexual And Reproductive Health