33911例新生儿听力联合耳聋基因筛查及随访结果的分析

目的通过分析新生儿听力联合耳聋基因筛查的结果,以及对阳性病例的随访和管理,提高遗传性耳聋的检出率。方法收集33911例新生儿听力联合耳聋基因筛查的结果,应用Sanger测序对听力未通过或基因筛查提示阳性的患儿进行验证。结果听力初筛通过率为93.32%,复筛为87.01%。耳聋基因筛查阳性率为4.18%。GJB2、SLC26A4、GJB3和12SrRNA基因变异的检出率分别为1.98%、1.58%、0.37%和0.25%。共检出126例迟发性耳聋,84例药物性耳聋,4例GJB2纯合/复合杂合变异,5例SLC26A4纯合/复合杂合变异。联合筛查发现GJB2、SLC26A4、GJB3和12SrRNA单杂合变异者听力初筛和复筛未通过的比例分别为6.75%和2.61%、3.3%和1.2%、0.72%和0.14%、0.36%和0%。纯合/单基因复合杂合变异、单基因杂合变异、多基因复合杂合以及GJB3纯合变异组听力筛查未通过率明显高于阴性组,差异具有统计学意义。结论基因检测是对新生儿听力筛查很好的补充。对阳性患儿的追踪管理能够有效提高耳聋的诊断率,但基因筛查不能等同于诊断,应综合分析基因检测、听力筛查和影像学的结果,Sanger/二代测序可作为重要的补充检查手段。

Analysis of results of concurrent hearing and deafness genetic screening and follow up of 33911 newborns

Objective To analyze the results of concurrent hearing and deafness genetic screening and follow up of newborns.Methods In total 33911 babies born to 5 designated hospitals in Nanshan District of Shenzhen city from October 2017 to December 2019 were included.All subjects underwent concurrent hearing and deafness genetic screening covering 21 variants of 4 genes including GJB2,SLC26A4,GJB3 and Mt12SrRNA.For those with positive results,Sanger sequencing was carried out for confirmation.Results 93.32%subjects passed the first-round hearing screening,and 87.01%passed the recheck testing.The overall detection rate was 4.18%.The detection rates for GJB2,SLC26A4,GJB3 and Mt12srRNA variants were 1.98%,1.58%,0.37%and 0.25%,respectively.126 and 84 subjects were found with high risk for delayed-onset and drug-induced hearing loss,respectively.In addition,4 and 5 subjects were found to harbor homozygous/compound heterozygous variants of the GJB2 and SLC26A4 genes,respectively.Concurrent screening showed that subjects(with heterozygous variants)who did not passed the two round hearing test were as follows:GJB2 with 6.75%in the first round and 2.61%in the second round testing,SLC26A4(3.3%/1.2%),GJB3(0.72%/0.14%)and 12SrRNA(0.36%/Nil),respectively.Moreover,the No-pass rate in the subjects with homozygous or compound variants in single gene,heterozygous variant in single gene,heterozygous variant in multiple genes,and homozygous variant in GJB3 gene were significantly higher than the subjects with negative results of genetic screening.Conclusion Concurrent newborn genetic screening can enhance the effectiveness of hearing screening and enable earlier identification and intervention for children with hearing impairment.Follow-up can improve the diagnostic rate for children who are positive for the concurrent screening.Nevertheless,genetic and hearing screening cannot replace the diagnostic testing.It is necessary to conduct comprehensive analysis for the results of genetic and hearing screening and radiological examinations.Sanger sequencing and next-generation sequencing are critical for ascertain the diagnosis.