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dc.contributor.authorZafar, Saba
dc.contributor.authorShahzad, Mohsin
dc.contributor.authorIshaq, Rafaqat
dc.contributor.authorYousaf, Ayesha
dc.contributor.authorShaikh, Rehan S
dc.contributor.authorAkram, Javed
dc.contributor.authorAhmed, Zubair M
dc.contributor.authorRiazuddin, Saima
dc.date.accessioned2020-09-09T17:46:31Z
dc.date.available2020-09-09T17:46:31Z
dc.date.issued2020-08-22
dc.identifier.urihttp://hdl.handle.net/10713/13660
dc.description.abstractWe report the underlying genetic causes of prelingual hearing loss (HL) segregating in eight large consanguineous families, ascertained from the Punjab province of Pakistan. Exome sequencing followed by segregation analysis revealed seven potentially pathogenic variants, including four novel alleles c.257G>A, c.6083A>C, c.89A>G, and c.1249A>G of CLPP, CDH23, COL4A5, and LARS2, respectively. We also identified three previously reported HL-causing variants (c.4528C>T, c.35delG, and c.1219T>C) of MYO15A, GJB2, and TMPRSS3 segregating in four families. All identified variants were either absent or had very low frequencies in the control databases. Our in silico analyses and 3-dimensional (3D) molecular modeling support the deleterious impact of these variants on the encoded proteins. Variants identified in MYO15A, GJB2, TMPRSS3, and CDH23 were classified as "pathogenic" or "likely pathogenic", while the variants in CLPP and LARS2 fall in the category of "uncertain significance" based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) variant pathogenicity guidelines. This paper highlights the genetic diversity of hearing disorders in the Pakistani population and reports the identification of four novel mutations in four HL families.en_US
dc.description.urihttps://doi.org/10.3390/genes11090978en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofGenesen_US
dc.subjectPakistanen_US
dc.subjectgenetic heterogeneityen_US
dc.subjectgenetic testingen_US
dc.subjectprelingual hearing lossen_US
dc.subjectwhole-exome sequencingen_US
dc.titleNovel Mutations in CLPP, LARS2, CDH23, and COL4A5 and Identified in Familial Cases of Prelingual Hearing Lossen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/genes11090978
dc.identifier.pmid32842620
dc.source.volume11
dc.source.issue9
dc.source.countryUnited States
dc.source.countrySwitzerland


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