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dc.contributor.authorRichard, E.M.
dc.contributor.authorSantos-Cortez, R.L.P.
dc.contributor.authorFaridi, R.
dc.date.accessioned2019-03-29T14:47:39Z
dc.date.available2019-03-29T14:47:39Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85056725877&doi=10.1002%2fhumu.23666&partnerID=40&md5=c7c7e0c28535f8f8de80ff4cf515db58
dc.identifier.urihttp://hdl.handle.net/10713/8726
dc.description.abstractConsanguineous 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. © 2018 Wiley Periodicals, Inc.en_US
dc.description.sponsorshipThe authors would like to thank all the families for participating in the study. The authors thank A. M. Waryah, R. Yousaf, and S. Yousaf for their technical help. The authors also would like to thank the University of Washington Center for Mendelian Genomics. NIDCD/NIH extramural research grants (R56 DC011803 to S.R., R01 DC011651 to S.M.L, R01 DC003594 to S.M.L, R01 DC012564 to Z.M.A); and in part from Intramural Research Program of the National Institute on Deafness and Other Communication Disorders at the NIH (DC000039-20 to T.B.F. and DC000086 to R.J.M.); and Higher Education Commission of Pakistan (HEC). Genotyping and exome sequencing performed at the UWCMG was funded by the National Human Genome Research Institute and the National Heart, Lung and Blood Institute grant HG006493 (to D.A.N., M.J.B., and S.M.L.).en_US
dc.description.urihttps://dx.doi.org/10.1002/humu.23666en_US
dc.language.isoen_USen_US
dc.publisherJohn Wiley and Sons Inc.en_US
dc.relation.ispartofHuman Mutation
dc.subjectallelic heterogeneityen_US
dc.subjectautosomal recessive hearing lossen_US
dc.subjectDFNBen_US
dc.subjectgenetic spectrumen_US
dc.subjectpathogenic varianten_US
dc.subject.lcshDeafnessen_US
dc.subject.lcshPakistanen_US
dc.titleGlobal genetic insight contributed by consanguineous Pakistani families segregating hearing lossen_US
dc.typeArticleen_US
dc.identifier.doi10.1002/humu.23666
dc.identifier.pmid30303587


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