title: Identification of novel mutations in the KCNQ4 gene of patients with nonsyndromic deafness from Taiwan.
abstract: Ion channels play important roles in signal transduction and in the regulation of the ionic composition of intra- and extracellular fluids. Mutations in ion channels have long been thought to be responsible for some forms of hearing loss. Defects in KCNQ4, a voltage-gated potassium channel, are a cause of nonsyndromic sensorineural deafness type 2, an autosomal dominant form of progressive hearing loss. We present data of mutation analysis of KCNQ4 from 185 unrelated Taiwanese probands with nonsyndromic hearing loss. The analysis revealed three novel KCNQ4 mutations and many polymorphisms. The prevalence of KCNQ4 gene mutations in this study was 1.62% (3/185). The mutations include a missense mutation (F182L) and two silent mutations (R216R and T501T). The F182L missense mutation was located in the S3 domain of KCNQ4. The F182 residue of KCNQ4 is highly conserved in KCNQ4 among various species and is less conserved in all members of the KCNQ family. In addition, although R216R is a silent mutation and does not alter the content of amino acid residue, the neural network prediction system revealed that it can potentially create a novel splice donor site during transcription. This mutation might affect the protein structure of KCNQ4 and consequently the normal function of the K+ channel. Our data provide the first comprehensive analysis of the KCNQ4 gene in Taiwanese patients with nonsyndromic deafness.
authors.affiliation: Genetics Laboratory, Department of Biomedical Sciences, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC.
authors.forename: Ching-Chyuan
authors.initials: CC
authors.lastname: Su
authors.forename: Jiann-Jou
authors.initials: JJ
authors.lastname: Yang
authors.forename: Jia-Ching
authors.initials: JC
authors.lastname: Shieh
authors.forename: Mao-Chang
authors.initials: MC
authors.lastname: Su
authors.forename: Shuan-Yow
authors.initials: SY
authors.lastname: Li
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003638:Deafness / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D051656:KCNQ Potassium Channels / Q000235:genetics*; D008297:Male; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000378:metabolism; D022821:RNA Splice Sites / Q000235:genetics; D012720:Severity of Illness Index; D013624:Taiwan / Q000453:epidemiology
chemical_list: D007473:Ion Channels; D051656:KCNQ Potassium Channels; C117367:KCNQ4 protein, human; D015221:Potassium Channels; D022821:RNA Splice Sites