Cell death-inducing cytotoxicity in truncated KCNQ4 variants associated with DFNA2 hearing loss.

ABSTRACT: KCNQ4 encodes the homotetrameric voltage-dependent potassium ion channel Kv7.4, and is the causative gene for autosomal dominant nonsyndromic sensorineural hearing loss, DFNA2. Dominant-negative inhibition accounts for the observed dominant inheritance of many DFNA2-associated KCNQ4 variants. In addition, haploinsufficiency has been presumed as the pathological mechanism for truncated Kv7.4 variants lacking the C-terminal tetramerization region, as they are unlikely to exert a dominant-negative inhibitory effect. Such truncated Kv7.4 variants should result in relatively mild hearing loss when heterozygous; however, this is not always the case. In this study, we characterized Kv7.4Q71fs (c.211delC), Kv7.4W242X (c.725G>A) and Kv7.4A349fs (c.1044_1051del8) in heterologous expression systems a

SUBMITTER: Kojima T 

PROVIDER: S-EPMC8628632 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature