Homozygosity mapping reveals novel and known mutations in Pakistani families with inherited retinal dystrophies.

Détails

Ressource 1Télécharger: BIB_98B9377D4E4A.P001.pdf (1571.07 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_98B9377D4E4A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Homozygosity mapping reveals novel and known mutations in Pakistani families with inherited retinal dystrophies.
Périodique
Scientific Reports
Auteur(s)
Saqib M.A., Nikopoulos K., Ullah E., Sher Khan F., Iqbal J., Bibi R., Jarral A., Sajid S., Nishiguchi K.M., Venturini G., Ansar M., Rivolta C.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
5
Pages
9965
Langue
anglais
Notes
Publication types: Journal Article Publication Status: epublish
Résumé
Inherited retinal dystrophies are phenotypically and genetically heterogeneous. This extensive heterogeneity poses a challenge when performing molecular diagnosis of patients, especially in developing countries. In this study, we applied homozygosity mapping as a tool to reduce the complexity given by genetic heterogeneity and identify disease-causing variants in consanguineous Pakistani pedigrees. DNA samples from eight families with autosomal recessive retinal dystrophies were subjected to genome wide homozygosity mapping (seven by SNP arrays and one by STR markers) and genes comprised within the detected homozygous regions were analyzed by Sanger sequencing. All families displayed consistent autozygous genomic regions. Sequence analysis of candidate genes identified four previously-reported mutations in CNGB3, CNGA3, RHO, and PDE6A, as well as three novel mutations: c.2656C > T (p.L886F) in RPGRIP1, c.991G > C (p.G331R) in CNGA3, and c.413-1G > A (IVS6-1G > A) in CNGB1. This latter mutation impacted pre-mRNA splicing of CNGB1 by creating a -1 frameshift leading to a premature termination codon. In addition to better delineating the genetic landscape of inherited retinal dystrophies in Pakistan, our data confirm that combining homozygosity mapping and candidate gene sequencing is a powerful approach for mutation identification in populations where consanguineous unions are common.
Pubmed
Web of science
Open Access
Oui
Création de la notice
31/05/2015 9:31
Dernière modification de la notice
20/08/2019 16:00
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