非综合征耳聋患儿常见耳聋基因高通量筛查及家系分析

High-throughput screening and pedigree analysis of common deafness genes in children with non-syndromic hearing loss

目的 分析GJB2、GJB3、SLC26A4及mitochondrial DNA基因在非综合征耳聋患者中突变频率,为温州地区耳聋基因普筛或产前诊断提供依据。方法 选取2016年-2019年温州地区239例非综合征耳聋患者作为研究对象,应用PCR-芯片技术对常见耳聋基因9个位点进行筛查。结果 对239例耳聋患儿基因筛查分析发现突变76例(31. 8%)。其中以c. 235 del C位点突变最高26例(10. 9%),其次为c. 919 A> G突变15例(6. 3%)和m. 1555A> G突变11例(4. 6%)。通过家系分析发现42例有明确耳聋家族史(17. 6%);其中检测出耳聋基因异常家系22例(52. 4%)。此外,对11例药物性耳聋相关1555A> G突变患者进行家系评估显示家系耳聋平均外显率较低(26. 8%),呈散发性特征。结论 温州地区NSHI患者耳聋基因突变形式多样化,且呈散发性趋势。通过基因高通量筛查能了解本地区的耳聋基因的突变类型及频率,对本地区的遗传性耳聋防治工作具有指导意义。

Objective To analyze the mutation frequency of GJB2,GJB3,SLC2644 and mitochondrial DNA genes in patients with non-syndromic hearing loss(NSHI),and provide basis for general screening of deafness genes or prenatal diagnosis in W enzhou area.Methods A total of 239 NSHI from 2016 to 2019 were selected as research objects,and PCR-chip technology was used to screen 9 sites of common deafness genes.Results Gene screening analysis of 239 cases of deafness children revealed mutations in 76 cases(31.8%).Among them,c.235 del C mutation was the highest in 26 cases(10.9%),followed by 15(6.3%)with c.919 A>G mutation and 11(4.6%)with m.1555A>G mutation.Family analysis revealed a clear family history of deafness in 42 cases(17.6%)。Among them,22(52.4%)families with genetic abnormality of deafness were detected.In addition,the pedigree evaluation of 11 patients with drug-induced deafness associated with 1555A>G mutation showed that the penetrance of family deafness was low(26.8%)and sporadie occurrence.Conclusion The mutation of deaf-ness gene in NSHI patients in W enzhou area was diversified and sporadic.The mutation types and frequencies of local deafness genes can be understood through high-throughput gene screening,which is of guiding significance for the prevention and treal-ment of hereditary deafness in this region.