Abstract:
Hearing loss is the most common sensory deficit
in humans with causative variants in over 140 genes. With
few exceptions, however, the population-specific distribution
for many of the identified variants/genes is unclear.
Until recently, the extensive genetic and clinical heterogeneity
of deafness precluded comprehensive genetic analysis.
Here, using a custom capture panel (MiamiOtoGenes),
we undertook a targeted sequencing of 180 genes in a multi-ethnic cohort of 342 GJB2 mutation-negative
deaf probands from South Africa, Nigeria, Tunisia, Turkey,
Iran, India, Guatemala, and the United States (South
Florida). We detected causative DNA variants in 25 % of
multiplex and 7 % of simplex families. The detection rate
varied between 0 and 57 % based on ethnicity, with Guatemala
and Iran at the lower and higher end of the spectrum,
respectively. We detected causative variants within 27
genes without predominant recurring pathogenic variants.
The most commonly implicated genes include MYO15A,
SLC26A4, USH2A, MYO7A, MYO6, and TRIOBP. Overall, our study highlights the importance of family history and
generation of databases for multiple ethnically discrete
populations to improve our ability to detect and accurately
interpret genetic variants for pathogenicity.
