期刊
PLOS ONE
卷 10, 期 3, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0119806
关键词
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资金
- COMSATS Institute of Information Technology (CIIT)
- CIIT [16-64/CRGP/CIIT/IBD/12/919, 16-83/CRGP/CIIT/IBD/13/144, 16-82-CRGP-CIIT-IBD-13/145]
- Stichting Nederlands Oogheelkundig Onderzoek
- Nelly Reef Foundation
- Stichting ter Verbetering van het Lot der Blinden
- Gelderse Blinden Stichting
- Rotterdamse Stichting Blindenbelangen
- Stichting Blindenhulp
- Stichting A.F. Deutman Researchfonds Oogheelkunde
- Stichting voor Ooglijders
- Algemene Nederlandse Vereniging ter Voorkoming van Blindheid
- Landelijke Stichting voor Blinden en Slechtzienden
- Stichting Retina Nederland Fonds
- Novartis fund
- Foundation Fighting Blindness USA [C-GE-0811-0545-RAD01]
- Pakistan Academy of Sciences
- [PAS/I-9/Project]
Background Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD). Methods We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), congenital stationary night blindness (CSNB), or cone dystrophy (CD). We employed genome-wide single nucleotide polymorphism (SNP) array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS) of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families. Results Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1. Conclusions Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.
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