Objective: To investigate the whole sequence of SLC26A4 gene among 1552 deaf students from 21 regions of China with SLC26A4 hot spot mutation IVS7-2A > G and analyze the epidemiological state of enlarged-vestibular-aqueduct-syndrome (EVAS) related hearing loss in China.
Methods: DNA was extracted from peripheral blood of 1552 students from deaf and dumb school of 21 regions in China. The nationality of the 1552 cases covers Han (1290 cases), Uigur (69 cases), Hui (37 cases), Mongolia (31 cases), Yi, Zhuang, Bai, Miao and other 13 nationalities (125 cases). Firstly, all subjects were analyzed for the hot spot mutation IVS7-2A > G by direct sequencing. Those carrying a single heterozygous IVS7-2A > G were given further analyzed for the probable second mutation in other exons except exon7 and exon8 of SLC26A4. One hundred and fifty cases with normal hearing were in the control group.
Results: The sequencing results revealed 197 cases carrying IVS7-2A > G, of whom 83 carrying IVS7-2A > G homozygous mutation, 114 carrying IVS7-2A > G heterozygous mutation. Of the 114 cases with heterozygous IVS7-2A > G, 78 cases were found to have another mutation and 36 cases were found no other mutation in SLC26A4. Of the 1552 cases, the percentage of cases carrying homozygous IVS7-2A > G and compound heterozygous mutations was 10.37% (161/1552). Of the 78 cases with SLC26A4 compound heterozygous mutations, the mutations except IVS7-2A > G were found mainly in exon 19, 10, 17, 15, 11 + 12, 14 and 3. Twenty-one novel SLC26A4 mutations were found. In the control group, there were only 3 cases carrying heterozygous IVS7-2A > G, and no other mutation in SLC26A4 was found.
Conclusions: SLC26A4 mutations account for at least 10% of EVAS related hereditary hearing loss in China. It's of great importance to screen SLC26A4 gene for making aetiological diagnosis for deafness. The discovery of novel variants of SLC26A4 gene makes the mutational and polymorphic spectrum more plentiful in Chinese population. We also provide preliminary evidence for the hot spot areas of SLC26A4.