当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY期刊下所有文献 > Identification of a novel mutation in SLC26A4 gene in a Chinese family with enlarged vestibular aqueduct syndrome.

Identification of a novel mutation in SLC26A4 gene in a Chinese family with enlarged vestibular aqueduct syndrome.

Abstract：

OBJECTIVE:To investigate the genetic causes of hearing loss in a two generation Chinese family with enlarged vestibular aqueduct syndrome (EVAS). METHODS:Clinical and genetic evaluations were conducted in a deaf proband and her normal-hearing parents. Sanger sequencing analysis of all the 21 exons, the exon-intron boundaries and the promoter in SLC26A4 gene was performed to detect the pathogenic mutations. PCR-restricted fragment length polymorphism (PCR-RFLP) was used to further identify the mutation. Phylogenetic analysis was carried out with multiple sequence alignment using BioEdit software. Three-dimensional (3D) modeling of the human wild-type and mutant SLC26A4 (NP_000432.1) was carried out using I-TASSER (http://zhanglab.ccmb.med.umich.edu/). RESULTS:Clinical examinations showed that the proband suffered from typical features of sensorineural hearing loss with enlarged vestibular aqueduct. A novel nonsense mutation c.2118C>A (p.C706X) in exon 19 was identified in compound heterozygosity with the splice-site mutation c.919-2A>G in the proband by using Sanger sequencing. The mother was a heterozygous carrier of c.919-2A>G in intron 7, while the father was a heterozygous carrier of c.2118C>A. The mutation c.2118C>A was not found in 200 unrelated controls using Sanger sequencing. PCR-RFLP showed the PCR product of the proband was not digested at 2110 by Fau I because of the c.2118C>A mutation. 3D-structure modeling indicated that the mutation c.2118C>A resulted in a truncate Pendrin protein. Protein alignment indicated high conservation of p.C706 residue in healthy Homo, Nomascus, Pan, Macaca, Canis, Sus, Mus, Rattus, Cricetulus and Xenopus. CONCLUSIONS:This study revealed a novel heterozygous mutation c.2118C>A (p.C706X) compound with c.919-2A>G in SLC26A4 gene in a patient with EVAS.

journal_name

Int J Pediatr Otorhinolaryngol

journal_title

International journal of pediatric otorhinolaryngology

authors

Zhang F,Bai X,Xiao Y,Zhang X,Zhang G,Li J,Xu L,Wang H

doi

10.1016/j.ijporl.2016.03.020

subject

Has Abstract

pub_date

2016-06-01 00:00:00

pages

75-9

eissn

0165-5876

issn

1872-8464

pii

S0165-5876(16)30013-1

journal_volume

pub_type

杂志文章

在线工具

Identification of a novel mutation in SLC26A4 gene in a Chinese family with enlarged vestibular aqueduct syndrome.