KCNQ4 mutations associated with nonsyndromic progressive sensorineural hearing loss.
OBJECTIVE
This article provides an update on the current progress in identification of KCNQ4 mutations responsible for DFNA2, a subtype of autosomal dominant nonsyndromic progressive hearing loss.


RESULTS
Hearing loss in pateints with DFNA2 usually start at high frequencies in their 20s and 30s, and then progress to more than 60 dB in less than 10 years, with middle and low frequencies often affected as well. To date, eight missense mutations and two deletions of the KCNQ4 gene have been identified in patients with DFNA2 with various clinical phenotypes. In general, missense mutations are associated with younger-onset and all-frequency hearing loss, whereas deletion mutations are underlying later-onset and pure high-frequency hearing loss. The etiology of DFNA2 remains largely unknown at this point, even though the degeneration of cochlear outer hair cells, caused by dysfunction of KCNQ4 channels, might be one of the underlying mechanisms.


CONCLUSIONS
During the last decade, significant progress has been made in identifying KCNQ4 mutations in patients with DFNA2. Elucidation of the pathogenic effect of these mutations will help to gain insights into the molecular mechanisms of hearing and hearing loss, which, in turn, will facilitate informative genetic counseling, early diagnosis, and even treatment of hearing loss.
Nie
Liping
L
Center for Neuroscience and Department of Otolaryngology-Head and Neck Surgery, University of California Davis, Davis, California 95618, USA. lnie@ucdavis.edu
D017668:Age of Onset; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006316:Hearing Loss, High-Frequency / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D015994:Incidence; D051656:KCNQ Potassium Channels / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D018570:Risk Assessment
D051656:KCNQ Potassium Channels; C117367:KCNQ4 protein, human
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