Mutations in potassium voltage‐gated channel subfamily Q member 4 (KCNQ4) are etiologically linked to nonsyndromic hearing loss (NSHL), deafness nonsyndromic autosomal dominant 2 (DFNA2). To identify causative mutations of hearing loss in 98 Korean families, we performed whole exome sequencing. In four independent families with NSHL, we identified a cosegregating heterozygous missense mutation, c.140T>C (p.Leu47Pro), in KCNQ4. Individuals with the c.140T>C KCNQ4 mutation shared a haplotype flanking the mutated nucleotide, suggesting that this mutation may have arisen from a common ancestor in Korea. The mutant KCNQ4 protein could reach the plasma membrane and interact with wild‐type (WT) KCNQ4, excluding a trafficking defect; however, it exhibited significantly decreased voltage‐gated potassium channel activity and fast deactivation kinetics compared with WT KCNQ4. In addition, when co‐expressed with WT KCNQ4, mutant KCNQ4 protein exerted a dominant‐negative effect. Interestingly, the channel activity of the p.Leu47Pro KCNQ4 protein was rescued by the KCNQ activators MaxiPost and zinc pyrithione. The c.140T>C (p.Leu47Pro) mutation in KCNQ4 causes progressive NSHL; however, the defective channel activity of the mutant protein can be rescued using channel activators. Hence, in individuals with the c.140T>C mutation, NSHL is potentially treatable, or its progression may be delayed by KCNQ activators.
Tibial lengthening with use of the Ilizarov external fixator over an intramedullary nail results in new bone formation of a quality equal to that obtained with the conventional Ilizarov method; however, it reduces the duration of external fixation and the rate of complications.
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