SLC26A4基因检测在儿童先天性内耳畸形早期诊断中的作用

Analysis the relationship between SLC26A4 mutation and current diagnosis of inner ear malformation in children with sensorineural hearing loss

目的:研究儿童感音神经性聋中SLC26A4基因致病性突变与先天性内耳畸形之间的关系,初步探讨SLC26A4基因检测在先天性耳聋早期病因诊断中作用。方法:按DNA测序的方法检测2 094例感音神经性聋患儿SLC26A4基因致病性突变情况,以Sennaroglu分类为标准统计以上患儿内耳CT表型情况,分析SLC26A4基因型与CT表型之间的关系。结果:12 094例患儿中,CT检查发现内耳畸形685例(耳蜗畸形371例中,Michel畸形6例,耳蜗未发育8例,共同腔畸形12例,IP-I畸形27例,耳蜗发育不全30例,Mondini畸形288例;大前庭水管265例;单纯前庭/半规管/内耳道畸形49例),内耳CT正常1 409例;2共检出SLC26A4基因致病性突变465例,其中双等位基因纯合突变135例,复合杂合突变330例;3SLC26A4基因致病性突变100%(465/465)在前庭水管扩大相关内耳畸形中检出。结论:SLC26A4基因致病性突变与前庭水管扩大相关内耳畸形密切相关,SLC26A4基因检测在儿童感音神经性聋早期病因诊断和干预方面具有一定的作用。

Objective：Explore the relationship between the pathogenic mutations of SLC26A4 gene and inner ear malformation,and analyze the feasibility of genetic testing to help current diagnosis in part of children with sensorineural hearing loss.Method：2094cases of children were detected by SLC26A4 with the method of DNA sequence.CT phenotypes of those children were classified according to the method proposed by Sennaroglu.We analyzed the relationship between the pathogenic mutations of gene and the CT phenotypes.Result：1685cases of inner ear malformations were found in 2094 cases of children with sensorineural hearing loss by CT examination（371cases of cochlea malformation were consisted of the follow types of malformation：Michel deformity was 6cases,cochlea aplasia was 8cases,common cavity deformity was 12 cases,incomplete partition type I was 27 cases,cochlea hypoplasia was 30 cases and Mondini malformation was 288cases）;Vestibular aqueduct was 265cases;Vestibular/semicircular canal/internal auditory canal were 49 cases,normal was 1409 cases.2The DNA sequence results revealed that 465 cases carried pathogenic mutations（Bi-allelic mutations）of SLC26A4 gene,among which 135 cases were homozygous,330 cases were compound heterozygous.3Pathogenic mutations of SLC26A4 gene detected 100%（465/465）in the group related to vestibular aqueduct malformation.Conclusion：The results suggest that pathogenic mutation of SLC26A4 gene is closely related to the CT phenotype of vestibular aqueduct malformation.Detecting of pathogenic mutations for hearing loss is binging the possibility to identify children with inner malformations at an early stage.As a consequence,it will improve the current diagnosis and therapeutical option.