摘要目的:探究一个罕见的前庭导水管扩大耳聋家系的致病基因变异类型，明确可能的遗传学病因。方法:应用全外显子组测序对一个听力障碍合并前庭导水管扩大的耳聋家系中的先证者进行基因检测，用Sanger测序法对侯选变异进行验证，并对先证者父母和弟弟进行检测。结果:先证者基因组DNA中检测到2个与常染色体隐性耳聋4型伴前庭导水管扩大相关的 FOXI1基因c.748dupG(p.Asp250Glyfs*30Asn)(致病，PVS1+PM2+PP4，尚未见报道)杂合变异和c.879C>A(p.Ser293Arg)(疑似致病，PM2+PM3+PP1+PP4，首次报道)杂合变异，先证者父母听力正常，分别为 FOXI1基因c.748dupG杂合变异和c.879C>A杂合变异携带者。先证者弟弟听力正常，携带 FOXI1基因c.748dupG杂合变异。 结论:该家系为一个罕见的 FOXI1基因复合杂合变异导致的常染色体隐性耳聋4型伴前庭导水管扩大耳聋家系， FOXI1基因c.748dupG和c.879C>A为新发现的变异，是该家系耳聋发生的遗传学病因，可以根据上述发现对家系进行遗传咨询和再发风险评估。

abstractsObjective:To explore the genetic basis for a Chinese pedigree affected with congenital deafness pedigree in conjunct with enlarged vestibular aqueduct.Methods:Whole-exome sequencing was carried out for the proband to analyze the genes associated with hereditary deafness. Candidate variant was verified by Sanger sequencing of the proband′s parents and her younger brother.Results:The proband was found to harbor compound heterozygous variants including c. 748dupG (p.Asp250Glyfs*30Asn) (pathogenic, PVS1+ PM2+ PP4) and c. 879C>A(p.Ser293Arg) (likely pathogenic, PM2+ PM3+ PP1+ PP4) of the FOXI1 gene, which has been associated with enlarged vestibular aqueduct (OMIM 600791). Both variants were unreported previously. The variants were respectively inherited from proband′s parents whom had normal hearing. Her younger brother was heterozygous for the c. 748dupG variant but also had normal hearing. Conclusion:The compound heterozygous variants of the FOXI1 gene probably underlay the pathogenicity of congenital deafness and enlarged vestibular aqueduct in the proband. The co-segregation of the two variants with the hearing loss has facilitated genetic counseling and prenatal diagnosis for this pedigree.