The Pathological Mechanisms of Hearing Loss Caused by <i>KCNQ1</i> and <i>KCNQ4</i> Variants
Deafness-associated genes <i>KCNQ1</i> (also associated with heart diseases) and <i>KCNQ4</i> (only associated with hearing loss) encode the homotetrameric voltage-gated potassium ion channels Kv7.1 and Kv7.4, respectively. To date, over 700 <i>KCNQ1</i> and over...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/9/2254 |
| Summary: | Deafness-associated genes <i>KCNQ1</i> (also associated with heart diseases) and <i>KCNQ4</i> (only associated with hearing loss) encode the homotetrameric voltage-gated potassium ion channels Kv7.1 and Kv7.4, respectively. To date, over 700 <i>KCNQ1</i> and over 70 <i>KCNQ4</i> variants have been identified in patients. The vast majority of these variants are inherited dominantly, and their pathogenicity is often explained by dominant-negative inhibition or haploinsufficiency. Our recent study unexpectedly identified cell-death-inducing cytotoxicity in several Kv7.1 and Kv7.4 variants. Elucidation of this cytotoxicity mechanism and identification of its modifiers (drugs) have great potential for aiding the development of a novel pharmacological strategy against many pathogenic <i>KCNQ</i> variants. The purpose of this review is to disseminate this emerging pathological role of Kv7 variants and to underscore the importance of experimentally characterizing disease-associated variants. |
|---|---|
| ISSN: | 2227-9059 |