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

Saqib, Muhammad Arif Nadeem and Nikopoulos, Konstantinos and Ullah, Ehsan and Sher Khan, Falak and Iqbal, Jamila and Bibi, Rabia and Jarral, Afeefa and Sajid, Sundus and Nishiguchi, Koji M. and Venturini, Giulia and Ansar, Muhammad and Rivolta, Carlo. (2015) Homozygosity mapping reveals novel and known mutations in Pakistani families with inherited retinal dystrophies. Scientific Reports, 5. 09965.

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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.
Faculties and Departments:03 Faculty of Medicine
09 Associated Institutions > Institute of Molecular and Clinical Ophthalmology Basel (IOB)
UniBasel Contributors:Rivolta, Carlo
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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edoc DOI:
Last Modified:03 Mar 2021 16:23
Deposited On:03 Mar 2021 16:23

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