5 296

Cited 7 times in

A novel synonymous mutation causing complete skipping of exon 16 in the SLC26A4 gene in a Korean family with hearing loss

Authors
 Yoonjung Kim  ;  Hui Ram Kim  ;  Juwon Kim  ;  Joong-Wook Shin  ;  Hong-Joon Park  ;  Jae Young Choi  ;  Un-Kyung Kim  ;  Kyung-A Lee 
Citation
 Biochemical and Biophysical Research Communications, Vol.430(3) : 1147-1150, 2013 
Journal Title
 Biochemical and Biophysical Research Communications 
ISSN
 0006-291X 
Issue Date
2013
Abstract
INTRODUCTION: Mutations in PDS (or SLC26A4) cause both Pendred syndrome (PS) and DFNB4, two autosomal recessive disorders that share hearing loss as a common feature. PS and DFNB4 are genetically homogeneous disorders caused by bi-allelic SLC26A4 mutations. Here, we report a novel synonymous mutation (c.1803G>A, p.Lys601Lys), that caused aberrant splicing in two Korean family members who were clinically considered to have DFNB4, along with congenital hearing loss and dilated vestibular aqueducts (DVA). METHODS: After extracting DNA from whole blood using standard procedures, the 21 exons and flanking introns of SLC26A4 were amplified with PCR. To evaluate the implication of a novel synonymous mutation (c.1803G>A), we used The Berkeley Drosophila Genome Project (BDGP) (http://www.fruitfly.org/) as a splice site prediction program and performed exon trapping analysis. RESULTS: In molecular analysis of the 21 exons of SCL26A4, we detected a known splicing mutation (c.919-2A>G, heterozygote) and a novel variant (c.1803G>A, heterozygote) in the patients (II-1 and II-2). According to in silico analysis, the novel variant (c.1803G>A) affects canonical splice donor nucleotide positioning. To define the transcript level effects of this novel 1803G>A variant, we performed exon trapping and confirmed that exon 16 is completely skipped in this variant type. CONCLUSION: We report a novel synonymous mutation (c.1803G>A) causing complete exon 16 skipping in the SLC26A4 gene in two Korean family members with hearing loss. This is the first case of a synonymous SNP (c.1803G>A) affecting vestibulocochlear organs through altering splicing accuracy by causing a complete skipping of exon 16. An important issue raised by this study is that synonymous mutations that have been previously ignored in clinical diagnoses must now be considered as potential pathogenic mutations.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X12023509
DOI
10.1016/j.bbrc.2012.12.022
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yoon Jung(김윤정) ORCID logo https://orcid.org/0000-0002-4370-4265
Kim, Ju Won(김주원)
Lee, Kyung A(이경아) ORCID logo https://orcid.org/0000-0001-5320-6705
Choi, Jae Young(최재영) ORCID logo https://orcid.org/0000-0001-9493-3458
Export
RIS (EndNote)
XLS (Excel)
XML
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86161
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse