Application of whole exome sequencing to Genetic Diagnosis in Families with Autosomal Recessive Non-syndromic Hearing Loss

Background: The genetic heterogeneity of non-syndromic hearing loss makes molecular diagnosis expensive andtime-consuming using tarditional techniques such as Sanger sequencing of DNA. Next-generation sequencing(NGS), provides a opportunity to identify candidate causative mutations in heterogeneous disease, such as hearingloss.Materials and Methods: After screening for mutations in GJB2, via Sanger sequencing, we performed wholeexome sequencing in proband 17 of Kho-4 family with autosomal recesive non-syndromic hearing loss(ARNSHL). Resulting data of the variants call format (VCF), were analysed and annotated using the DNAnexussoftware package and phenotype-based exome analysis tools. Then, bioinformatic analysis of variants were doneusing in Sillico software. Finally, we targeted 4 candidate genes for cosegregation via sanger sequencing.Results: We identified 63 candidate variants by analysing and annotating. Next, we targeted 9 genes (TMPRSS4,EPHA6, PTPRH, CPA3, LENG1, NLRP7, NXN, ZNF530, ZNF594) by in sillica tools. Finally, the result of Sangersequencing did not confirm cosegregation of variants in PTPRH, TMPRSS4, EPHA6, CPA3 in Kho-4 family.Conclusions: Targeted next-generation sequencing allows suggesting new candidate mutation genes for causinghearing loss.

کلیدواژه ها:

Hearing loss ، Kho-4 family ، NGS