title: Correlation between genotype and phenotype in patients with bi-allelic SLC26A4 mutations.
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 (EVA) and hearing loss. p.H723R (61%), c.919-2A>G (24%), and p.T410M (4%) were the most common mutations in Korean patients with EVAs. 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.
authors.affiliation: Department of Otorhinolaryngology; BK21 Project for Medical Science.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Jung
authors.forename: J W
authors.initials: JW
authors.lastname: Shin
authors.forename: M H
authors.initials: MH
authors.lastname: Song
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: J-H
authors.initials: JH
authors.lastname: Lee
authors.forename: K-A
authors.initials: KA
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Shin
authors.forename: U-K
authors.initials: UK
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Bok
authors.forename: K-Y
authors.initials: KY
authors.lastname: Lee
authors.forename: J Y
authors.initials: JY
authors.lastname: Choi
authors.forename: H J
authors.initials: HJ
authors.lastname: Park
mesh_terms: D003638:Deafness / Q000235:genetics* / Q000473:pathology*; D005787:Gene Frequency; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D056910:Republic of Korea; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000473:pathology
chemical_list: D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters
keywords: Mondini dysplasia; RNA splicing; anion exchanger; pendred syndrome