Comprehensive molecular analysis of 61 Egyptian families with hereditary nonsyndromic hearing loss

Abstract

Nonsyndromic hearing loss is an extremely heterogeneous disorder. Thus, clinical diagnostics is challenging, in particular due to differences in the etiology of hearing loss between populations. With this study, we wanted to elucidate the genetic basis of hearing loss in 61 consanguineous Egyptian families. In 25 families, linkage analysis was used as a prescreening to identify regions for targeted sequencing of candidate genes. Initially, the coding regions of 12 and later of 94 genes associated with hearing loss were enriched and subjected to massively parallel sequencing (MPS) with diagnostic yields of 36% and 75%, respectively. Causative variants were identified in 48 families (79%). They were found in 23 different genes with the majority being located in MYO15A (15.3%), SLC26A4 (9.7%), GJB2 (8.3%), and MYO7A (6.4%). As many as 32 variants were novel ones at the time of detection. Five variants were shared by two, three, or even four families. Our study provides a first survey of the mutational spectrum of deaf patients in Egypt revealing less GJB2 variants than in many European populations. It underlines the value of targeted enrichment of well‐selected deafness genes in combination with MPS in the diagnostics of this frequent and genetically heterogeneous disorder.

Identification of Novel Compound Heterozygous MYO15A Mutations in Two Chinese Families with Autosomal Recessive Nonsyndromic Hearing Loss

“…The mutation c.6340G>A of the MYO15A gene, a known path-ogenic missense mutation, leads to an alternation of a Valine with a Methionine at amino acid position 2114 in the MyTH4 domain. The c.6340G>A mutation was previously reported in another Chinese family and in two Egyptian families which is predicted to weaken the function of MyTH4 [15,16]. It was predicted as deleterious by computational tools.…”

Prevalence and Characteristics of STRC Gene Mutations (DFNB16): A Systematic Review and Meta-Analysis

“…To estimate the stability of outcomes, we conducted sensitivity analyses by assessing the effects of removing low-quality publications (Francey et al, 2012 ; Chang and Choi, 2014 ; Gu et al, 2015 ; Vona et al, 2015 ; Bademci et al, 2016 ; Mehta et al, 2016 ; Sommen et al, 2016 ; Baux et al, 2017 ; Zazo Seco et al, 2017 ; Cabanillas et al, 2018 ; Guan et al, 2018 ; Marková et al, 2018 ; Sheppard et al, 2018 ; Back et al, 2019 ; Budde et al, 2020 ; Downie et al, 2020 ; Kim et al, 2020 ; Safka Brozkova et al, 2020 ). The summary prevalence of DFNB16 in non-GJB2 HL patients was 3.98% (95% CI: 0.0260–0.0606, I 2 = 70%, p < 0.01), which stabilized the findings in the range of that of crude analysis.…”

“…The estimated pooled prevalence in the mild–moderate HI group was 50.71% (95% CI: 0.2813–0.7300) and that of the other-HI group was 9.44% (95% CI: 0.0620–0.1412) ( Supplementary Figure 2B ). Sensitivity analyses were completed by assessing the effects of deleting low-quality studies (Chang and Choi, 2014 ; Bademci et al, 2016 ; Mehta et al, 2016 ; Sommen et al, 2016 ; Baux et al, 2017 ; Zazo Seco et al, 2017 ; Cabanillas et al, 2018 ; Guan et al, 2018 ; Sheppard et al, 2018 ; Budde et al, 2020 ; Downie et al, 2020 ; Kim et al, 2020 ; Safka Brozkova et al, 2020 ). The summary prevalence of DFNB16 in genetically confirmed (non-GJB2) HL patients was 9.63% (95% CI: 0.0558–0.1614, I 2 = 80%, p < 0.01) in the sensitivity analysis and without apparent fluctuation.…”

Comprehensive medical evaluation of pediatric bilateral sensorineural hearing loss

“… 41 These stepwise genetic testing strategies may be more cost effective and help avoid WGS and WES in circumstances where they are not necessary. 44 , 45 , 46 , 47 Other alternatives include the use of targeted sequencing or microarray testing if a syndromic cause is suspected. 48 Targeted sequencing can test for a set of mutations or genes known to cause the suspected syndrome.…”