Dataset Information

Expanding Genotype-Phenotype Correlation of CLCNKA and CLCNKB Variants Linked to Hearing Loss.

ABSTRACT: The ClC-K channels CLCNKA and CLCNKB are crucial for the transepithelial transport processes required for sufficient urinary concentrations and sensory mechanoelectrical transduction in the cochlea. Loss-of-function alleles in these channels are associated with various clinical phenotypes, ranging from hypokalemic alkalosis to sensorineural hearing loss (SNHL) accompanied by severe renal conditions, i.e., Bartter's syndrome. Using a stepwise genetic approach encompassing whole-genome sequencing (WGS), we identified one family with compound heterozygous variants in the ClC-K channels, specifically a truncating variant in CLCNKA in trans with a contiguous deletion of CLCNKA and CLCNKB. Breakpoint PCR and Sanger sequencing elucidated the breakpoint junctions derived from WGS, and allele-specific droplet digital PCR confirmed one copy loss of the CLCNKA_CLCNKB contiguous deletion. The proband that harbors the CLCNKA_CLCNKB variants is characterized by SNHL without hypokalemic alkalosis and renal anomalies, suggesting a distinct phenotype in the ClC-K channels in whom SNHL predominantly occurs. These results expanded genotypes and phenotypes associated with ClC-K channels, including the disease entities associated with non-syndromic hearing loss. Repeated identification of deletions across various extents of CLCNKA_CLCNKB suggests a mutational hotspot allele, highlighting the need for an in-depth analysis of the CLCNKA_CLCNKB intergenic region, especially in undiagnosed SNHL patients with a single hit in CLCNKA.

SUBMITTER: Yun Y

PROVIDER: S-EPMC10707517 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Expanding Genotype-Phenotype Correlation of CLCNKA and CLCNKB Variants Linked to Hearing Loss.

Yun Yejin Y Park Sang Soo SS Lee Soyoung S Seok Heeyoung H Park Seongyeol S Lee Sang-Yeon SY

International journal of molecular sciences 20231203 23

The ClC-K channels CLCNKA and CLCNKB are crucial for the transepithelial transport processes required for sufficient urinary concentrations and sensory mechanoelectrical transduction in the cochlea. Loss-of-function alleles in these channels are associated with various clinical phenotypes, ranging from hypokalemic alkalosis to sensorineural hearing loss (SNHL) accompanied by severe renal conditions, i.e., Bartter's syndrome. Using a stepwise genetic approach encompassing whole-geno ...[more]

PMID: 38069401

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Dataset Information

Expanding Genotype-Phenotype Correlation of CLCNKA and CLCNKB Variants Linked to Hearing Loss.

Publications

Expanding Genotype-Phenotype Correlation of <i>CLCNKA</i> and <i>CLCNKB</i> Variants Linked to Hearing Loss.

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