An ancient founder mutation in PROKR2 impairs human reproduction.

Details

Ressource 1Download: serval:BIB_6D77B428DE1B.P001 (282.13 [Ko])
State: Public
Version: author
License: Not specified
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_6D77B428DE1B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
An ancient founder mutation in PROKR2 impairs human reproduction.
Journal
Human Molecular Genetics
Author(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
Publication state
Published
Issued date
2012
Volume
21
Number
19
Pages
4314-4324
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
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
Yes
Create date
23/11/2012 21:40
Last modification date
25/09/2019 6:09
Usage data