Objective: 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.