An ancient founder mutation in PROKR2 impairs human reproduction.

Détails

Ressource 1Télécharger: serval:BIB_6D77B428DE1B.P001 (282.13 [Ko])
Etat: Public
Version: de l'auteur
Licence: Non spécifiée
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ID Serval
serval:BIB_6D77B428DE1B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
An ancient founder mutation in PROKR2 impairs human reproduction.
Périodique
Human Molecular Genetics
Auteur(s)
Avbelj Stefanija M., Jeanpierre M., Sykiotis G.P., Young J., Quinton R., Abreu A.P., Plummer L., Au M.G., Balasubramanian R., Dwyer A.A., Florez J.C., Cheetham T., Pearce S.H., Purushothaman R., Schinzel A., Pugeat M., Jacobson-Dickman E.E., Ten S., Latronico A.C., Gusella J.F., Dode C., Crowley W.F., Pitteloud N.
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Statut éditorial
Publié
Date de publication
2012
Volume
21
Numéro
19
Pages
4314-4324
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Congenital gonadotropin-releasing hormone (GnRH) deficiency manifests as absent or incomplete sexual maturation and infertility. Although the disease exhibits marked locus and allelic heterogeneity, with the causal mutations being both rare and private, one causal mutation in the prokineticin receptor, PROKR2 L173R, appears unusually prevalent among GnRH-deficient patients of diverse geographic and ethnic origins. To track the genetic ancestry of PROKR2 L173R, haplotype mapping was performed in 22 unrelated patients with GnRH deficiency carrying L173R and their 30 first-degree relatives. The mutation's age was estimated using a haplotype-decay model. Thirteen subjects were informative and in all of them the mutation was present on the same ~123 kb haplotype whose population frequency is ≤10%. Thus, PROKR2 L173R represents a founder mutation whose age is estimated at approximately 9000 years. Inheritance of PROKR2 L173R-associated GnRH deficiency was complex with highly variable penetrance among carriers, influenced by additional mutations in the other PROKR2 allele (recessive inheritance) or another gene (digenicity). The paradoxical identification of an ancient founder mutation that impairs reproduction has intriguing implications for the inheritance mechanisms of PROKR2 L173R-associated GnRH deficiency and for the relevant processes of evolutionary selection, including potential selective advantages of mutation carriers in genes affecting reproduction.
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/11/2012 22:40
Dernière modification de la notice
25/09/2019 7:09
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