[Genetic and prenatal diagnosis of a Chinese pedigree with autosomal recessive Wolfram syndrome 1 due to compound heterozygous variants of WFS1 gene].

OBJECTIVE: To explore the genetic pathogenicity for a Chinese pedigree affected with severe syndromic deafness. METHODS: High-throughput sequencing was carried out to analyze the 415 genes associated with hereditary deafness in the proband who has hearing loss in association with optic atrophy and hyperglycemia. Candidate variants were verified by Sanger sequencing of the proband, her parents and the fetus. RESULTS: The proband was found to harbor compound heterozygous variants of WFS1 gene, namely c.2389G>A (p.Asp797Asn) and c.2345C>T (p.Pro782Leu), which was known to underlie Wolfram syndrome 1. The proband's parents had normal hearing and were both heterozygous carriers for the above variants. The fetus was found to harbor the same compound heterozygous variants and was predicted to have a high risk. CONCLUSION: The compound heterozygous variants of c.2389G>A and c.2345C>T of the WFS1 gene probably underlay the pathogenesis of hearing loss in the proband. Above finding has facilitated genetic counseling and prenatal diagnosis for this family.