先天性内耳畸形与SLC26A4基因相关性的研究

Analysis on correlation between gene mutations(SLC26A4) and congenital malformations of inner ear

目的分析婴幼儿、儿童先天性感音神经性聋(sensorineural hearing loss,SNHL)中先天性内耳畸形患儿的SLC26A4基因突变发生的概率,突变类型以及基因突变与各种内耳畸形之间的关系。方法回顾性分析125例(225耳)先天性内耳畸形的SNHL患儿的影像学及听力学资料,收集其中77例先天性内耳畸形患儿及正常对照组100例的外周血。提取基因组DNA,聚合酶链反应扩增SLC26A4,直接测序分析突变。结果 77例样本中79.2%(42/53)的前庭导水管扩大组、90%(9/10)的Mondini畸形组、7.1%(1/14)其他内耳畸形组中的患者发现有SLC26A4基因突变。共发现SLC26A4基因突变类型16种,其中4种为新发现的类型。69.8%(44/63)前庭导水管扩大(enlarged vestibular aqueduct,EVA)和Mondini畸形组中发现c.919-2A>G(IVS7-2A>G)突变,等位基因突变频率50%(63/126),是SLC26A4基因最常见的突变类型。EVA组和Mondini组分别与正常对照组等位基因突变频率比较差异有显著性(P=0.000,P<0.01)。结论 SLC26A4基因突变是EVA和Mondini畸形的主要原因之一,c.919-2A>G(IVS7-2A>G)是最常见的突变类型。

OBJECTIVE To analyze the correlation between gene mutations（SLC26A4）and congenital malformations of inner ear in pediatric patients with sensorineural hearing loss（SNHL）.METHODS Imaging and auditory data of 125 cases（225ears）in pediatric patients with congenital SNHL were retrospectively studied.Peripheral blood samples were collected from 77 pediatric patients with congenital malformations of inner ear and 100 hearing normal controls,retrospectively.Genomic DNA was extracted from the blood;direct sequencing were used to detect the mutations of SLC26A4 gene.RESULTS SLC26A4 mutations were detected in 79.2%（42/53）of the patients with enlarged vestibular aqueduct（EVA）,90%（9/10）of the patients with Mondini deformity of inner ear,and 7.1%（1/14）of the patients with other malformations of inner ear.c.9192AG（IVS7-2AG）mutation was the most prevalent mutation of SLC26A4 gene,accounting for 69.8%（43/63）in patients with EVA and Mondini deformity and 50%（63/126）of mutant alleles.16 kinds of different SLC26A4 mutations were identified,4 of which had never been previously reported.However,there was significant difference between EVA group and controls（P =0.000,P0.01）,as well as between Mondini deformity group and controls（P=0.000,P0.01）.CONCLUSION Mutations in the SLC26A4 gene are a major cause of EVA and Mondini deformity.The distribution in the degree of hearing loss in patients with CT scan anomalies and two SLC26A4 mutations was not different from that in patients with one or zero mutations.