59例大前庭导水管综合征SLC26A4基因突变频率及新发突变位点分析

Analysis of 59 cases of large vestibular aqueduct syndrome SLC26A4gene mutation frequency and new mutation sites

目的:研究云南地区前庭导水管扩大耳聋患儿SLC26A4基因突变位点频率,报道SLC26A4基因新发突变位点,进一步明确SLC26A4基因突变谱,探讨SLC26A4基因的双等位、单等位基因突变与内耳CT表型的关联,为耳聋的临床和基因诊断提供依据。方法:回顾2016年8月至2021年9月昆明市儿童医院耳鼻喉科390例人工耳蜗术后患儿颞骨CT检查结果,对59例发现前庭导水管扩大的患儿进行对SLC26A4基因Sanger测序,并将行颞骨CT检查的患儿按照基因检测结果分为SLC26A4双等位基因突变组(纯合突变和复合杂合突变)、单等位基因突变组,分析与内耳CT表型的关联,并对新发位点进行总结分析。结果:在390例人工耳蜗植入患儿中,发现前庭导水管扩大患儿59例,其中48例(81.4%)检测出SLC26A4基因突变,其中SLC26A4双等位基因突变46例,包括纯合突变16例,复合杂合突变30例,SLC26A4单等位基因突变2例;11例(18.6%)前庭导水管扩大患儿未检测到SLC26A4基因突变。在48例可检测到SLC26A4基因突变的前庭导水管扩大耳聋患儿中,共检出36种SLC26A4基因突变,突变位点以c.919-2A>G最为常见,其次常见位点为c.1174A>T、c.2168A>G。检测发现3个突变位点为国际上尚未报道的突变,分别为c.312_322delATATGCCCTAC2例,c.304+3A>C1例,c.100C>T1例,突变类型分别为移码突变、剪切突变、无义突变,突变位点均经Sanger测序证实。48例前庭导水管扩大患儿颞骨CT检查,大前庭水管综合征(enlargedvestibularaqueductsyndrome,EVAS)合并Mondini畸形33例,单独EVAS15例,未见单独Mondini畸形。结论:伴SLC26A4基因突变的前庭导水管扩大耳聋患儿以c.919-2A>G突变最常见,发现3种SLC26A4基因的新变异;CT检查联合基因检测发现,一部分前庭导水管扩大患儿与SLC26A4单等位基因突变或未检测到SLC26A4基因突变相关,提示有待研究EVAS的其他致病机制。

Objective:To study the frequency of SLC26A4 gene mutation sites in children with enlarged vestibular aqueduct deafness in Yunnan,report the new mutation sites of SLC26A4 gene,further clarify the mutation spectrum of SLC26A4gene,and explore the association between biallelic and monoallelic mutations of SLC26A4 gene and CT phenotype of inner ear,so as to provide basis for clinical and genetic diagnosis of deafness.Methods:Review the results of temporal bone CT examination of 390 children after cochlear implantation in the Department of Otolaryngology,Kunming Children's Hospital from August 2016 to September 2021.Sanger sequencing of SLC26A4 gene was performed in 59 children with enlarged vestibular aqueduct.According to the genetic test results,the children who underwent temporal bone CT examination were divided into two groups:SLC26A4 biallelic mutation group(homozygous mutation and compound heterozygous mutation),monoallelic mutation group,and the association with inner ear CT phenotype was analyzed,and the new sites were summarized and analyzed.Results:The c.919-2a>g mutation was the most common mutation in children with enlarged vestibular aqueduct with SLC26A4 gene mutation.Three new variants of SLC26A4 gene were found;CT examination combined with genetic testing found that a part of children with enlarged vestibular aqueduct was associated with SLC26A4 monoallelic mutation or no SLC26A4 gene mutation was detected.Further research is needed to investigate the involvement of other pathogenic factors in the pathogenesis of EVA.