Molecular Etiology of Hearing Impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis

Pu Dai,Xiuhui Zhu,Dongyang Kang,Huijun Yuan,Fei Yu,Lee-Jun C Wong,Yongyi Yuan,Deliang Huang,Bailin Wu,Dongyi Han

doi:10.1186/1479-5876-6-74

Abstract

BackgroundThe molecular etiology of hearing impairment in Chinese has not been thoroughly investigated. Study of GJB2 gene revealed that 30.4% of the patients with hearing loss in Inner Mongolia carried GJB2 mutations. The SLC26A4 gene mutations and relevant phenotype are analyzed in this study.MethodsOne hundred and thirty-five deaf patients were included. The coding exons of SLC26A4 gene were sequence analyzed in 111 patients, not including 22 patients carrying bi-allelic GJB2 mutations or one patient carrying a known GJB2 dominant mutation as well as one patient with mtDNA 1555A>G mutation. All patients with SLC26A4 mutations or variants were subjected to high resolution temporal bone CT scan and those with confirmed enlarged vestibular aqueduct and/or other inner ear malformation were then given further ultrasound scan of thyroid and thyroid hormone assays.ResultsTwenty-six patients (19.26%, 26/135) were found carrying SLC26A4 mutation. Among them, 17 patients with bi-allelic SLC26A4 mutations were all confirmed to have EVA or other inner ear malformation by CT scan. Nine patients were heterozygous for one SLC26A4 mutation, including 3 confirmed to be EVA or EVA and Mondini dysplasia by CT scan. The most common mutation, IVS7-2A>G, accounted for 58.14% (25/43) of all SLC26A4 mutant alleles. The shape and function of thyroid were confirmed to be normal by thyroid ultrasound scan and thyroid hormone assays in 19 of the 20 patients with EVA or other inner ear malformation except one who had cystoid change in the right side of thyroid. No Pendred syndrome was diagnosed.ConclusionIn Inner Mongolia, China, mutations in SLC26A4 gene account for about 12.6% (17/135) of the patients with hearing loss. Together with GJB2 (23/135), SLC26A4 are the two most commonly mutated genes causing deafness in this region. Pendred syndrome is not detected in this deaf population. We established a new strategy that detects SLC26A4 mutations prior to the temporal bone CT scan to find EVA and inner ear malformation patients. This model has a unique advantage in epidemiologic study of large deaf population.

Highlights

Every year in China, about 30,000 children, compared to 840 in UK and one of every one thousand infants in US, are born with congenital hearing impairment[1,2,3]
The IVS7-2A>G mutation accounts for 58.14% (25/43, counting only the definite pathogenic and most likely pathogenic variants) of all SLC26A4 mutant alleles (Table 1). These results suggest that a significant proportion (26/135 = 19.26%) of Chinese hearing impairment has molecular defects in SLC26A4
We found that SLC26A4 mutations were detected in nearly 20% of our patients with hearing impairment with IVS7-2A>G being the most prevalent mutation

Summary

Introduction

Every year in China, about 30,000 children, compared to 840 in UK and one of every one thousand infants in US, are born with congenital hearing impairment[1,2,3]. Hearing impairment is the most common neurosensory disorder in human that has an incidence of approximately 1 in 1000 children worldwide[4]. The most common molecular defects for nonsyndromic autosomal recessive deafness lie on Connexin 26, a gap junction protein encoded by the GJB2[5,6,7,8,9,10,11,12]. More than 150 mutations, polymorphisms and unclassified variants have been described in GJB2 to account for about 8–40% of molecular etiology of the patients with nonsyndromic hearing impairment http:// davinci.crg.es/deafness[3]. About 80% of the patients with nonsyndromic hereditary deafness in China do not have mutations in GJB2[13]. Study of GJB2 gene revealed that 30.4% of the patients with hearing loss in Inner Mongolia carried GJB2 mutations. The SLC26A4 gene mutations and relevant phenotype are analyzed in this study

Methods

Results

Discussion

Conclusion