Investigation of the genetic cause of hearing loss in Newfoundland families

Penney, Cindy (2018) Investigation of the genetic cause of hearing loss in Newfoundland families. Masters thesis, Memorial University of Newfoundland.

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Abstract

The purpose of this study was to determine the genetic cause of hearing loss in a seven-generation Newfoundland family. Twenty-nine family members were recruited segregating autosomal dominant hearing loss. Genome-wide SNP genotyping and linkage analysis showed significant linkage (LOD=4.77) to chromosome 13q34. The region contained 26 genes and a known deafness locus (DFNA33). Exome sequencing identified 13 variants of interest within the linked region, but only 3 co-segregated with hearing loss: F10 c.865+26C>T, ADPRHL1 c.380-17C>A and c.380-16T>G. All three were absent from 81 population controls, yet the ADPRHL1 c.380-17C>A and c.380-16T>G were identified in two other probands with hearing loss. All three were predicted to affect splicing of nearby exons, however cDNA analysis of ADPRHL1 showed no effect. F10 c.865+26C>T, ADPRHL1 c.380-17C>A and c.380-16T>G are rare, co-segregate with hearing loss, and are possibly pathogenic. Conversely, they may help form a disease haplotype and exist in linkage disequilibrium with the causal mutation. However, the putative ADPRHL1 variants have been found in multiple families with hearing loss and further investigations are necessary to elucidate their effect.

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