Abstract
BackgroundHearing Impairment (HI) can have genetic or environmental causes and in some cases, an interplay of both. Genetic causes are difficult to determine as mutations in more than 90 genes have been shown recently to be responsible for HI. Providing a genetic diagnostic test for HI is therefore a challenge especially for ethnic groups where GJB2 mutations are shown to be rare.ResultsHere we show the design and implementation of an amplicon-based targeted sequencing panel that allows the simultaneous sequencing of 87 HI genes. Mutations identified included known pathogenic mutations and novel variants with unknown significance. The diagnostic rate of this panel is 28 % when only pathogenic variants were reported. However, an additional 28 % harbored recurrent combinations of novel or rare single nucleotide variants in the OTOF or PCDH15 genes. Such combinations were not identified in healthy individuals.ConclusionsTargeted sequencing approach is a very useful strategy for the identification of mutations affecting the HI genes because of its relatively fast turn-around time and cost effectiveness compared to whole-exome sequencing. Further novel or rare variants could be identified by implementing a large-scale screening of HI using our panel which will eventual lead to a higher diagnostic rate.
Highlights
Hearing Impairment (HI) can have genetic or environmental causes and in some cases, an interplay of both
Targeted sequencing approach is a very useful strategy for the identification of mutations affecting the HI genes because of its relatively fast turn-around time and cost effectiveness compared to whole-exome sequencing
Further novel or rare variants could be identified by implementing a large-scale screening of HI using our panel which will eventual lead to a higher diagnostic rate
Summary
Hearing Impairment (HI) can have genetic or environmental causes and in some cases, an interplay of both. Genetic causes are difficult to determine as mutations in more than 90 genes have been shown recently to be responsible for HI. The large number of genes required for hearing causes such complexity in inheritance patterns. Mutations in any one of such genes is sufficient to cause various degrees of HI. Mutations in GJB2, SLC26A4, MYO15A, OTOF, and CDH23 genes are the most frequent causes of autosomal recessive HI at varying degrees [2]. About 50 % of any given cohort of autosomal recessive HI will have a pathogenic mutation in the GJB2 gene [3,4,5,6]. The frequency of HI-causing GJB2 gene mutations is
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