Bi-allelic Pro291Leu variant in KCNQ4 leads to early onset non-syndromic hearing loss.


School of Biological Sciences, University of the Punjab, Quaid-i-Azam campus, Lahore 54590, Pakistan. Electronic address: [Email]


Variants of KCNQ4 are one of the most common causes of dominantly inherited nonsyndromic hearing loss. We investigated a consanguineous family in which two individuals had prelignual hearing loss, apparently inherited in a recessive mode. Whole-exome sequencing analyses demonstrated genetic heterogeneity as variants in two different genes segregated with the phenotype in two branches of the family. Members in one branch were homozygous for a pathogenic variant of TMC1. The other two affected individuals were homozygous for a missense pathogenic variant in KCNQ4 c.872C>T; p.(Pro291Leu). These two individuals had prelingual, progressive moderate to severe hearing loss, while a heterozygous carrier had late onset mild hearing loss. Our work demonstrates that p.Pro291L variant is semi-dominantly inherited. This is the first report of semi-dominance of a KCNQ4 variant.


ADNSHL,ARNSHL,BHCMG,Baylor-Hopkins Center for Mendelian Genomics,DFNA2A,Deafness,Hearing loss,KCNQ4,Pakistan,WES,Whole exome sequencing,

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