Targeted Next-Generation Sequencing of a Deafness Gene Panel (MiamiOtoGenes) Analysis in Families Unsuitable for Linkage Analysis

Abstract

Hearing loss (HL) is a common sensory disorder in humans with high genetic heterogeneity. To date, over 145 loci have been identified to cause nonsyndromic deafness. Furthermore, there are countless families unsuitable for the conventional linkage analysis. In the present study, we used a custom capture panel (MiamiOtoGenes) to target sequence 180 deafness-associated genes in 5 GJB2 negative deaf probands with autosomal recessive nonsyndromic HL from Iran. In these 5 families, we detected one reported and six novel mutations in 5 different deafness autosomal recessive (DFNB) genes (TRIOBP, LHFPL5, CDH23, PCDH15, and MYO7A). The custom capture panel in our study provided an efficient and comprehensive diagnosis for known deafness genes in small families.

High‐throughput custom capture sequencing identifies novel mutations in coloboma‐associated genes: Mutation in DNA‐binding domain of retinoic acid receptor beta affects nuclear localization causing ocular coloboma

“…Custom capture or targeted gene sequencing has been a cost‐effective approach to detect mutations in genes known to be associated with a specific disease condition (Aparisi et al, ; Bonachea et al, ; Patel et al, ; Rehm, ; Shang et al, ; Trujillano et al, ; X. Wang et al, ). Previous studies exploring mutations in coloboma‐associated genes have been limited to a subset of genes in affected families (Gonzalez‐Rodriguez et al, ; Williamson & FitzPatrick, ).…”

“…Custom capture or targeted gene sequencing has been a cost-effective approach to detect mutations in genes known to be associated with a specific disease condition (Aparisi et al, 2014;Bonachea et al, 2014;Patel et al, 2018;Rehm, 2013;Shang et al, 2018;Trujillano et al, 2014; X. Wang et al, 2016).…”

Screening Consanguineous Families for Hearing Loss Using the MiamiOtoGenes Panel

“…A previously reported stopgain variant (c.4936C>T; p.R1646X) (Wesdrop, 2017) in LOXHD1 (NM_144612.6; NP_653213.6) was identified in family KF-18. A previously reported splice variant (Schrauwen et al, 2012) c.637 + 1G>T in CABP2 (NM_016366.3; (Shang et al, 2018). A novel missense variant c.1190C>T (p.A397V), predicted to be pathogenic, was identified in MYO7A in KF-2.…”

“…Patients homozygous for R1746Q have been reported show symptoms of ''atypical Usher syndrome'' with variable retinal phenotypes (Bolz et al, 2001;Astuto et al, 2002). In the Iranian population, 13 missense and 2 splice CDH23 mutations have been identified (Sloan-Heggen et al, 2015;Bademci et al, 2016;Ghasemnejad et al, 2017;Shang et al, 2018). The stopgain variant USH1C c.628A>T (p.K210X) in KF-4 has been previously observed only in a Turkish family (Bademci et al, 2016).…”

Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next‐generation sequencing

“…To date, over 30 point mutations have been reported in the TRIOBP gene. Previous studies have suggested exon 7 of TRIOBP as a hotspot for mutations, probably due to presence of repetitive sequences 32,34 . The protein contains two types of domains, N‐terminal pleckstrin homology (PH) and C‐terminal coiled‐coil.…”