Molecular Analysis of Twelve Pakistani Families with Nonsyndromic or Syndromic Hearing Loss.

AIM: To investigate the causative genetic mutations in 12 Pakistani families with nonsyndromic or syndromic hearing loss.

METHODS: Mutations in the most common causative gene for hearing loss, GJB2, were evaluated by Sanger sequencing. Targeted next-generation sequencing or whole-exome sequencing was used to analyze the genomic DNA samples from 11 probands with hearing loss. Sanger sequencing was performed to verify all identified variants.

RESULTS: We found pathogenic, or likely to be pathogenic, mutations in all 12 families, including six known mutations in GJB2, SLC26A4, LHFPL5, and USH2A and eight novel mutations in ESPN, MYO7A, LRTOMT, PCDH15, USH2A, or EPS8L2. Notably, four compound heterozygous mutations in the MYO7A and USH2A genes were detected in two consanguineous families. In addition, the novel frameshift mutation in EPS8L2 was first documented in Pakistan.

CONCLUSIONS: Our study increases the spectrum of mutations associated with hearing loss in the Pakistani population. In addition, our study highlights the fact that compound heterozygous mutations, although rare, can occur in consanguineous families.