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目的:对4个耳聋家系进行遗传性耳聋基因变异的筛查，为家系遗传咨询与产前诊断提供依据。方法:应用二代测序技术对家系先证者进行耳聋基因检测，并对可疑基因变异采用Sanger双向测序对先证者及家系成员进行验证，确定可疑致病变异后，对3个家系高危胎儿进行产前诊断。结果:家系1先证者检测到n TMC1基因c.100C>T(p.R34X)和c.642＋4A>C复合杂合变异，家系2先证者检测到n TMC1基因c.582G>A(p.W194X)和c．589G>A(p.G197R)复合杂合变异，家系3先证者检测到n TMC1基因c.1396_1398delAAC和c.1571T>C(p.F524S)复合杂合变异，家系4先证者检测到n TMC1基因c.2050G>C(p.D684H)纯合变异，4个家系先证者父母均为携带者，其中c.642＋4A>C、c.1571T>C(p.F524S)变异位点既往未见报道；产前诊断结果显示3个家系胎儿均不是患者，出生后随访至2019年9月，听力未见异常。n 结论:TMC1基因变异是4个耳聋家系的可能致病原因，分子生物学的发现增加了对n TMC1基因功能的认识并丰富了人类基因变异数据库，为家系遗传咨询和产前诊断提供了依据。n “,”Objective:To explore the genetic basis of four Chinese families affected with deafness.Methods:All probands were subjected to next generation sequencing (NGS). Suspected variant were verified by Sanger sequencing among the family members. Prenatal diagnosis was provided for three couples through Sanger sequencing.Results:All probands were found to carry pathogenic variants of the n TMC1 gene, which included c. 100C>T (p.R34X) and c. 642+ 4A>C in family 1, c. 582G>A (p.W194X) and c. 589G>A (p.G197R) in family 2, c. 1396_1398delAAC and c. 1571T>C (p.F524S) in family 3, and homozygosity of c. 2050G>C (p.D684H) in family 4. All parents were heterozygous carriers of the variants. The c. 642+ 4A>C and c. 1571T>C (p.F524S) were unreported previously. Prenatal diagnosis revealed that none of the fetuses were affected. Follow-up confirmed that all newborns had normal hearing.n Conclusion:Variant of the TMC1 gene probably underlay the deafness in the four families. Above findings have enhanced our understanding of the function of the n TMC1 gene and enriched its variant spectrum. The results also facilitated genetic counseling and prenatal diagnosis for the families.n