KCNQ4 基因中 Pro291Leu 错义双等位变异导致早发性非综合征型听力损失。
Bi-allelic Pro291Leu variant in KCNQ4 leads to early onset non-syndromic hearing loss.
机构信息
School of Biological Sciences, University of the Punjab, Quaid-i-Azam campus, Lahore 54590, Pakistan.
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA; Baylor-Hopkins Center for Mendelian Genomics, Baltimore, MD, USA.
出版信息
Gene. 2019 Jul 15;705:109-112. doi: 10.1016/j.gene.2019.04.064. Epub 2019 Apr 24.
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.
KCNQ4 变体是最常见的显性遗传性非综合征性听力损失原因之一。我们研究了一个近亲结婚的家庭，其中有两个人表现出前语言听力损失，显然是隐性遗传模式。全外显子组测序分析表明存在遗传异质性，因为两个不同基因中的变体在家族的两个分支中与表型分离。一个分支的成员纯合携带 TMC1 的致病性变体。另外两名受影响的个体纯合携带 KCNQ4 c.872C>T 错义致病性变体；p.(Pro291Leu)。这两个人表现出前语言、进行性中度至重度听力损失，而杂合携带者则表现出迟发性轻度听力损失。我们的工作表明，p.Pro291L 变体是半显性遗传的。这是 KCNQ4 变体半显性遗传的首次报道。
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