Mutation analysis of SLC26A4 in mainland Chinese patients with enlarged vestibular aqueduct.
OBJECTIVE
We have characterized the spectrum of SLC26A4 mutations and clinical features in a population of mainland Chinese patients with nonsyndromic sensorineural hearing loss (SNHL) and enlarged vestibular aqueduct (EVA).


METHODS
Cross-sectional clinical genetic study.


METHODS
Tertiary care outpatient otolaryngology clinic.


METHODS
A total of 32 subjects identified with bilateral EVA using high-resolution CT were screened for mutations in SLC26A4 by denaturing high-performance liquid chromatography and direct sequencing methods.


RESULTS
A total of 13 different mutations were identified in the SLC26A4 gene, five of which are novel. A total of 88 percent of the patients harbored biallelic mutations, 11 patients were homozygotes, and 17 were compound heterozygotes. Four patients were found to carry a single SLC26A4 mutation. The IVS7-2A>G mutation was the most frequent, accounting for 60 percent of the mutant alleles. We have not found any correlations between the type of SLC26A4 mutations and the type, degree, and progression of hearing loss. There are significant proportions of patients with asymmetric (26%), progressive (32%), or fluctuating hearing loss (21%).


CONCLUSIONS
Our data confirm the high prevalence of SLC26A4 mutations in Chinese patients with SNHL and EVA. We could not establish any relationship between genotype and phenotype. However, the high incidence of asymmetric, progressive, and fluctuating hearing loss found in the current study indicates that patients with those features should be routinely screened for SLC26A4 mutation in addition to diagnosis of EVA using CT or MRI.
Department of Otolaryngology, University of Miami, Miami, FL 33136, USA.
Samuel
S
Reyes
Guojian
G
Wang
Xiaomei
X
Ouyang
Bing
B
Han
Li Lin
LL
Du
Hui Jun
HJ
Yuan
Denise
D
Yan
Pu
P
Dai
Xue-Zhong
XZ
Liu
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002680:Chin; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D011859:Radiography; D017422:Sequence Analysis, DNA; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000000981:diagnostic imaging / Q000473:pathology*; D055815:Young Adult
D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters