Genetic diagnosis of a pedigree affected with Usher syndrome type 1D/F / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a pedigree affected with congenital sensorineural deafness.@*METHODS@#High-throughput sequencing was carried out to analyze the coding regions of 415 genes associated with hereditary deafness in the proband. Suspected variants were verified by PCR amplification and Sanger sequencing of her parents and sister.@*RESULTS@#The proband was found to have carried a heterozygous c.5131G>A (p.Val1711Ile) variant of the CDH23 gene and a heterozygous c.2884C>T(p.Arg962Cys) variant of the PCDH15 gene, which were respectively inherited from her mother and father. Her sister (with normal hearing) was also heterozygous for the c.5131G>A (p.Val1711Ile) variant of the CDH23 gene but not the c.2884C>T (p.Arg962Cys) variant of the PCDH15 gene. Based on the guidelines of the American College of Medical Genetics and Genomics, both variants were predicted to be likely pathogenic (PS1+PM2+PP3+PP4).@*CONCLUSION@#The c.5131G>A (p.Val1711Ile) variant of the CDH23 gene and c.2884C>T (p.Arg962Cys) variant of the PCDH15 gene probably underlay the pathogenesis of Usher syndrome type 1D/F in this pedigree.