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

Memoona Ramzan, Hafiza Idrees, Ghulam Mujtaba, Nara Sobreira, P. Dane Witmer, Sadaf Naz

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)109-112
Number of pages4
JournalGene
Volume705
DOIs
StatePublished - Jul 15 2019

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Keywords

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

ASJC Scopus subject areas

  • Genetics

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