The role of next generation sequencing in predicting hearing loss

Skarżyńśki, Henryk

doi:10.1080/14737159.2021.1902313

Cited by 3 publications

(2 citation statements)

References 16 publications

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“…There are other ways to establish an etiological diagnosis, however. Three commonly used testing strategies (custom targeted next-generation sequencing panel-based testing, whole exome sequencing and whole genome sequencing) all have their own advantages and disadvantages, which we summarized in Table 3 [26][27][28][29][30][31]. Partly based on these evolutions, we recommend re-evaluating patients with unidentified hearing loss on a regular basis, in addition to the more frequent audiological follow-up.…”

Section: Discussionmentioning

confidence: 99%

Negative Molecular Diagnostics in Non-Syndromic Hearing Loss: What Next?

Clabout

Maes

Acke

et al. 2022

Genes

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Congenital hearing loss has an impact on almost every facet of life. In more than 50% of cases, a genetic cause can be identified. Currently, extensive genetic testing is available, although the etiology of some patients with obvious familial hearing loss remains unknown. We selected a cohort of mutation-negative patients to optimize the diagnostic yield for genetic hearing impairment. In this retrospective study, 21 patients (17 families) with negative molecular diagnostics for non-syndromic hearing loss (gene panel analysis) were included based on a positive family history with a similar type of hearing loss. Additional genetic testing was performed using a whole exome sequencing panel (WESHL panel v2.0) in four families with the strongest likelihood of genetic hearing impairment. In this cohort (n = 21), the severity of hearing loss was most commonly moderate (52%). Additional genetic testing revealed pathogenic copy number variants in the STRC gene in two families. In summary, regular re-evaluation of hearing loss patients with presumably genetic etiology after negative molecular diagnostics is recommended, as we might miss newly discovered deafness genes. The switch from gene panel analysis to whole exome sequencing or whole genome sequencing for the testing of congenital hearing loss seems promising.

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Section: Discussionmentioning

confidence: 99%

Negative Molecular Diagnostics in Non-Syndromic Hearing Loss: What Next?

Clabout

Maes

Acke

et al. 2022

Genes

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“…Genetic factors are suggested to be the single largest independent predictor of postoperative outcomes [6,20]. With technological progression occurring rapidly, and cochlear implantation being provided to patients with residual hearing, there is a demand for extensive genetic testing in patients not just for cochlear implant candidacy, but also as a mechanism to understand natural hearing loss progression, the expected degree of natural hearing preservation, and outcomes to various auditory rehabilitation strategies [21]. As demonstrated in our study, sensory and neural partition pathogenic variants may help provide useful post-operative information for patients, however the molecular mechanisms underlying the genes and variants involved in non-syndromic hearing loss add additional complexity when understanding post-operative implications.…”

Section: Plos Onementioning

confidence: 99%

Gene mutations as a non-invasive measure of adult cochlear implant performance: Variable outcomes in patients with select TMPRSS3 mutations

Cottrell,

Dixon,

Cao

et al. 2023

PLoS ONE

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Background The cochlear implant (CI) has proven to be a successful treatment for patients with severe-to-profound sensorineural hearing loss, however outcome variance exists. We sought to evaluate particular mutations discovered in previously established sensory and neural partition genes and compare post-operative CI outcomes. Materials and methods Utilizing a prospective cohort study design, blood samples collected from adult patients with non-syndromic hearing loss undergoing CI were tested for 54 genes of interest with high-throughput sequencing. Patients were categorized as having a pathogenic variant in the sensory partition, pathogenic variant in the neural partition, pathogenic variant in both sensory and neural partition, or with no variant identified. Speech perception performance was assessed pre- and 12 months post-operatively. Performance measures were compared to genetic mutation and variant status utilizing a Wilcoxon rank sum test, with P<0.05 considered statistically significant. Results Thirty-six cochlear implant patients underwent genetic testing and speech understanding measurements. Of the 54 genes that were interrogated, three patients (8.3%) demonstrated a pathogenic mutation in the neural partition (within TMPRSS3 genes), one patient (2.8%) demonstrated a pathogenic mutation in the sensory partition (within the POU4F3 genes). In addition, 3 patients (8.3%) had an isolated neural partition variance of unknown significance (VUS), 5 patients (13.9%) had an isolated sensory partition VUS, 1 patient (2.8%) had a variant in both neural and sensory partition, and 23 patients (63.9%) had no mutation or variant identified. There was no statistically significant difference in speech perception scores between patients with sensory or neural partition pathogenic mutations or VUS. Variable performance was found within patients with TMPRSS3 gene mutations. Conclusion The impact of genetic mutations on post-operative outcomes in CI patients was heterogenous. Future research and dissemination of mutations and subsequent CI performance is warranted to elucidate exact mutations within target genes providing the best non-invasive prognostic capability.

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Segregation of Trans Mutations in the CDH23 Gene in an Emirati Family with Sensorineural Hearing Loss

Alsebeyi,

Mutery,

Tehsil Gul

et al. 2024

Genes

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Background/Objectives: Hearing loss (HL) is a significant global health concern, affecting approximately 1 in every 1000 newborns, with over half of these cases attributed to genetic factors. This study focuses on identifying the genetic basis of autosomal recessive non-syndromic hearing loss (ARNSHL) in a consanguineous Emirati family. Methods: Clinical exome sequencing (CES) was performed on affected members of the family, followed by Sanger sequencing to validate the findings. Specific primers were used for PCR amplification of target CDH23 exons. Mutations were analyzed using various computational tools to assess their pathogenicity. Results: We identified two heterozygous mutations in the CDH23 gene: a novel nonsense variant (c.264G>A, p.Trp88Ter) and a missense variant (c.5168G>A, p.Arg1723His). Both mutations were found in trans configuration, suggesting a compound heterozygous state contributing to the phenotype. In silico analysis predicted a significant impact on protein function, potentially leading to the observed ARNSHL. Conclusions: This study emphasizes the complexity of genetic factors in hearing loss, particularly in highly consanguineous populations. The identification of both nonsense and missense mutations in the CDH23 gene enhances understanding of its role in hearing loss and provides essential insights for genetic counseling and future therapeutic strategies.

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The role of next generation sequencing in predicting hearing loss

Cited by 3 publications

References 16 publications

Negative Molecular Diagnostics in Non-Syndromic Hearing Loss: What Next?

Negative Molecular Diagnostics in Non-Syndromic Hearing Loss: What Next?

Gene mutations as a non-invasive measure of adult cochlear implant performance: Variable outcomes in patients with select TMPRSS3 mutations

Segregation of Trans Mutations in the CDH23 Gene in an Emirati Family with Sensorineural Hearing Loss

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