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.

Int J Pediatr Otorhinolaryngol. 2016 Jun;85:75-9

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

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://ift.tt/1roobKN).
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.

PMID: 27240500 [PubMed - in process]

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