Investigation Of SLC26A4 Gene In Patients Associated With Sensorineural Hearing Loss In Northwest China

Large vestibular aqueduct syndrome (LVAS) is a common autosomal recessive and non-syndromic deafness, which acounts for nearly 1-12% in the children associated with sensorineural hearing loss. The patients clinically characterized by fluctuating or progressive sensorineural hearing loss, and the hearing loss level is common in high-tone frequencies. Most patients were identified with biallelic deafness, someone mixed with vestibular dysfunction. The onset age of patients varies from birth to adolescence, mostly in childhood. The disease is found suddenly or hiddenly, often appeared after a cold, a mild cranial trauma, a sexual trauma or a history of intracranial hypertension.The locus responsible for this disorder, SLC26A4 gene, has been mapped to chromosome 7q31 by Abe et al in 1999. SLC26A4 gene has an extensive mutation map spreading over all the exon and their flanking sequences, most of them are missense mutations, in addition to frameshift mutations, splice site mutations, insertions or deletions that lead to a stop codon. Up to date, more than 200 of SLC26A4 mutations have been described in different countries and ethnic groups. Investigation of this gene has been carried out by many researches. In this study, we collected deaf students from school for deafmutes in Shaanxi, Ningxia province and sporadic outpatients from the 2nd hospital of Lanzhou University, in addition to original researches. The following report is:PartⅠ: Hereditary feature of SLC26A4 mutations in families associated with large vestibular aqueduct syndromeFive families associated with LVAS were recruited in this study, including three simplex families and two multiplex families. All of the 21 exons of SLC26A4 including the flanking sequences were amplified by the polymerase chain reaction (PCR) with genomic DNA. As a result, a total of 4 different types of mutations were found, with 2 reported mutations (c.919-2A>G and c.2168A>G) and 2 novel mutations (c.232T>C and c.2006A>T).8 patients were identified with biallelic mutations, while their parents with normal hearing were detected with monoallelic mutation. SLC26A4 mutations transmitted solidly from the parents to offspring, the probability of patients were higher than the theoretical value (25%).Part II:Investigation of hotspot in SLC26A4 gene in 2423 patients associated with sensorineural hearing loss in Northwest ChinaIn this study, exons 8 and 19 in SLC26A4 gene were detected in 2423 patients associated with severe-profound sensorineural hearing loss. A total of 277 (11.4%) patients were detected with either biallelic or monoallelic mutations,10 different types of mutations were identified, including 3 reported mutations (c.919-2A>G, c.2168A>G and c.2162C＞T) and 7 novel mutations (c.919-18T>G, c.920C＞T, c.987A>G, c.1001+5G>C, c.1001+32A>G, c.2107C＞G and c.2183A>G).c.919-2A>G and c.2168A>G were two most prevalent mutations. We also found that statistically significant differences in c.919-2A>G and c.2168A>G between Han and Uigur, and the statistical difference in c.919-2A>G was also found between Hui and Uigur. HRCT scan were performed on 17 patients with biallelic mutations and 8 patients with monoallelic mutation. All patients with biallelic mutations had EVA, however, one subject with monoallelic mutation showed normal inner ear.