Show simple item record

dc.contributor.authorIshaq, R.
dc.contributor.authorAhmed, Z.M.
dc.contributor.authorRiazuddin, S.
dc.date.accessioned2019-12-25T18:07:11Z
dc.date.available2019-12-25T18:07:11Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85076490485&doi=10.3390%2fgenes10121031&partnerID=40&md5=74b911b424d0a98711f1e54b07daba0b
dc.identifier.urihttp://hdl.handle.net/10713/11543
dc.description.abstractHearing loss is a genetically heterogeneous disorder affecting approximately 360 million people worldwide and is among the most common sensorineural disorders. Here, we report a genetic analysis of seven large consanguineous families segregating prelingual sensorineural hearing loss. Whole-exome sequencing (WES) revealed seven different pathogenic variants segregating with hearing loss in these families, three novel variants (c.1204G>A, c.322G>T, and c.5587C>T) in TMPRSS3, ESRRB, and OTOF, and four previously reported variants (c.208C>T, c.6371G>A, c.226G>A, and c.494C>T) in LRTOMT, MYO15A, KCNE1, and LHFPL5, respectively. All identified variants had very low frequencies in the control databases and were predicted to have pathogenic effects on the encoded proteins. In addition to being familial, we also found intersibship locus heterogeneity in the evaluated families. The known pathogenic c.226C>T variant identified in KCNE1 only segregates with the hearing loss phenotype in a subset of affected members of the family GCNF21. This study further highlights the challenges of identifying disease-causing variants for highly heterogeneous disorders and reports the identification of three novel and four previously reported variants in seven known deafness genes. Copyright 2019 by the authors.en_US
dc.description.sponsorshipThis study has been supported by grants from the National Institutes of Health (NIH), National Institute on Deafness and Other Communication Disorders (NIDCD) No. R56DC011803 (to S.R.) and No. R01DC016295 (to Z.M.A.).en_US
dc.description.urihttps://doi.org/10.3390/genes10121031en_US
dc.language.isoen_USen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofGenes
dc.subjectGenetic heterogeneityen_US
dc.subjectGenetic testingen_US
dc.subjectIntra-familial heterogeneityen_US
dc.subjectPrelingual hearing lossen_US
dc.subjectWhole-exome sequencingen_US
dc.titleDelineation of homozygous variants associated with prelingual sensorineural hearing loss in Pakistani familiesen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/genes10121031
dc.identifier.pmid31835641


This item appears in the following Collection(s)

Show simple item record