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Gene ; 705: 109-112, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31028865

RESUMO

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.


Assuntos
Surdez/genética , Sequenciamento do Exoma/métodos , Canais de Potássio KCNQ/genética , Mutação de Sentido Incorreto , Idade de Início , Consanguinidade , Feminino , Heterogeneidade Genética , Predisposição Genética para Doença , Humanos , Leucina/genética , Masculino , Linhagem , Prolina/genética
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