The genetic etiology of early-onset hearing loss in Newfoundland and Labrador

Squires, Jessica (2015) The genetic etiology of early-onset hearing loss in Newfoundland and Labrador. Masters thesis, Memorial University of Newfoundland.

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Abstract

Hearing loss is the most common sensory disorder worldwide and > 50% of cases can be attributed to single gene mutations. I used a targeted candidate gene approach and Sanger sequencing to screen genomic DNA from 101 deaf probands with Newfoundland ancestry for pathogenic mutations in deafness genes. First I screened for mutations in WFS1, TMPRSS3, and PCDH15 that were previously identified in this population, then for mutations in Cx26 and Cx30, and mutations in the mitochondrial genes MTRNR1 and MTTS1. Finally, genes were targeted based on patterns of hearing loss as seen on patient audiograms. Although several probands were “solved” by this approach, none had mutations in WFS1, TMPRSS3 or PCDH15. One proband had digenic mutations in Cx26 and Cx30 and two probands inherited the A1555G mutation in MTRNR1. In order to decipher several variants of unknown pathogenicity and solve more families, further clinical recruitment and whole genome approaches are required.

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