A novel frameshift mutation of POU4F3 gene associated with autosomal dominant non-syndromic hearing loss.
Autosomal dominant mutations in the transcription factor POU4F3 gene are associated with non-syndromic hearing loss in humans; however, there have been few reports of mutations in this gene worldwide. We performed a mutation analysis of the POU4F3 gene in 42 unrelated Koreans with autosomal dominant non-syndromic hearing loss, identifying a novel 14-bp deletion mutation in exon 2 (c.662del14) in one patient. Audiometric examination revealed severe bilateral sensorineural hearing loss in this patient. The novel mutation led to a truncated protein that lacked both functional POU domains. We further investigated the functional distinction between wild-type and mutant POU4F3 proteins using in vitro assays. The wild-type protein was completely localized in the nucleus, while the truncation of protein seriously affected its nuclear localization. In addition, the mutant failed to activate reporter gene expression. This is the first report of a POU4F3 mutation in Asia, and moreover our data suggest that further investigation will need to delineate ethnicity-specific genetic background for autosomal dominant non-syndromic hearing loss within Asian populations.
Lee
Hee Keun
HK
Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
Park
Hong-Joon
HJ
Lee
Kyu-Yup
KY
Park
Rekil
R
Kim
Un-Kyung
UK
D044466:Asian People / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D016368:Frameshift Mutation; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D056910:Republic of Korea; D050821:Transcription Factor Brn-3C / Q000235:genetics*
D018398:Homeodomain Proteins; C111223:POU4F3 protein, human; D050821:Transcription Factor Brn-3C