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Global genetic insight contributed by consanguineous Pakistani families segregating hearing loss
Author(s) -
Richard Elodie M.,
SantosCortez Regie Lyn P.,
Faridi Rabia,
Rehman Atteeq U.,
Lee Kwanghyuk,
Shahzad Mohsin,
Acharya Anushree,
Khan Asma A.,
Imtiaz Ayesha,
Chakchouk Imen,
Takla Christina,
Abbe Izoduwa,
Rafeeq Maria,
Liaqat Khurram,
Chaudhry Taimur,
Bamshad Michael J.,
Nickerson Deborah A.,
Schrauwen Isabelle,
Khan Shaheen N.,
Morell Robert J.,
Zafar Saba,
Ansar Muhammad,
Ahmed Zubair M.,
Ahmad Wasim,
Riazuddin Sheikh,
Friedman Thomas B.,
Leal Suzanne M.,
Riazuddin Saima
Publication year - 2019
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23666
Subject(s) - biology , genetics , pedigree chart , sanger sequencing , exome sequencing , genotyping , exome , gene , hearing loss , disease gene identification , consanguinity , genetic heterogeneity , population , genotype , dna sequencing , mutation , medicine , phenotype , audiology , environmental health
Consanguineous Pakistani pedigrees segregating deafness have contributed decisively to the discovery of 31 of the 68 genes associated with nonsyndromic autosomal recessive hearing loss (HL) worldwide. In this study, we utilized genome‐wide genotyping, Sanger and exome sequencing to identify 163 DNA variants in 41 previously reported HL genes segregating in 321 Pakistani families. Of these, 70 (42.9%) variants identified in 29 genes are novel. As expected from genetic studies of disorders segregating in consanguineous families, the majority of affected individuals (94.4%) are homozygous for HL‐associated variants, with the other variants being compound heterozygotes. The five most common HL genes in the Pakistani population are SLC26A4 , MYO7A , GJB2 , CIB2 and HGF , respectively. Our study provides a profile of the genetic etiology of HL in Pakistani families, which will allow for the development of more efficient genetic diagnostic tools, aid in accurate genetic counseling, and guide application of future gene‐based therapies. These findings are also valuable in interpreting pathogenicity of variants that are potentially associated with HL in individuals of all ancestries. The Pakistani population, and its infrastructure for studying human genetics, will continue to be valuable to gene discovery for HL and other inherited disorders.