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چکیده
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Introduction Next generation sequencing (NGS) is in the frontier of testing strategies through which the whole genome or part of it (Whole exome sequencing and targeted enrichment panels) is examined rapidly and efficiently. NGS offers opportunity to solve the dilemma of extreme genetically heterogeneous diseases such as deafness. Autosomal recessive non-syndromic hearing loss (ARNSHL) is the most common form of hearing loss with the involvement of at least 50 genes. In this study, NGS was used to elucidate the genetic etiology of ARNSHL in families from Iran. Materials and methods Totally, 20 large multiplex consanguineous ARNSHL families collected from Khuzestan and Kohkiloyeh & Boyrahamad provinces of Iran were recruited. GJB2 mutations (by Sanger sequencing) and a panel of 10-15 genes (by genetic linkage analysis) had been investigated on them and were found to be negative for their involvement. NGS was performed using either Otogenetics deafness panel including 129 genes or whole exome sequencing with 50X vertical coverage. A bioinformatics analysis pipeline was optimized at tertiary analysis level for annotation and prioritization of variants. Results NGS panel and exome sequencing revealed pathogenic variants in 6 out of 10 and 5 out of 10 samples, respectively. Conclusion Totally, 55% of etiology was clarified at this stage using NGS. Trio exome sequencing, SNP array and whole genome sequencing are being considered for the remaining families. Our results suggest a diagnostic algorithm for diagnosis of deafness in Iran.
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