Correlation between genotype and phenotype in patients with bi-allelic SLC26A4 mutations
Other Titles
SLC26A4 유전자의 이중대립형질 돌연변이를 가진 환자들의 유전형과 표현형의 상관관계
Authors
신중욱
Department
Dept. of Otorhinolaryngology (이비인후과학교실)
Issue Date
2014
Description
Dept. of Medicine/박사
Abstract
Mutation of SLC26A4 is the most common cause of prelingual hearing loss in East Asia. Patients with SLC26A4 mutations have variable phenotypes ranging from non-syndromic hearing loss to Pendred syndrome. Here, we analyzed the correlation between genotype and various inner ear phenotypes and found a possible underlying mechanism. This study included 111 patients with bi-allelic SLC26A4 mutations who had bilateral enlarged vestibular aqueduct and hearing loss. p.H723R (61%), c.919-2A>G (24%), and p.T410M (4%) were the most common mutations in Korean patients with enlarged vestibular aqueducts. Residual hearing in patients with c.919-2A>G or p.T410M mutations was better than that of patients with p.H723R homozygous mutations. Interestingly, quantitative polymerase chain reaction showed normal pendrin transcript (6-17% of normal levels) was produced from patients with c.919-2A>G homozygous mutations. Surface expression ratio of pendrin and residual anion exchange activity were higher in cells transfected with p.T410M in comparison to cells transfected with p.H723R. These results suggest that there is a correlation between degree of residual hearing and the SLC26A4 genotype commonly found in the East Asian population. In case of some specific mutants such as c.919-2A>G or p.T410M, pharmacological interventions to sustain residual pendrin activity may allow patients to have better hearing ability.