Clinical features of hearing loss caused by STRC gene deletions/mutations in Russian population

Маркова, Т Г; Alekseeva, N. N.; Миронович, О. Л.; Галеева, Н. М.; Lalayants, M. R.; Bliznetz, E. A.; Чибисова, С. С.; Polyakov, A. V.; Таварткиладзе, Г. А.

doi:10.1016/j.ijporl.2020.110247

Cited by 13 publications

(7 citation statements)

References 34 publications

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“…Conversely, STRC SNVs have been reported only in a few cohorts [ 12 ] due to the complexity of interpretation of STRC sequencing data secondary to the presence of p- STRC . Despite the fact that a detailed genotype–phenotype correlation between STRC loss-of-function and mild-to-moderate HL has been reported in studies involving a limited number of participants, this correspondence seems extremely consistent in all of them [ 4 , 37 , 38 , 39 ]. In this light, diagnostic tools able to highlight point mutations in this gene overcoming the pseudogene issue should be implemented in all laboratories specialised in the diagnostic work-up of HHL.…”

Section: Discussionmentioning

confidence: 97%

The Enigmatic Genetic Landscape of Hereditary Hearing Loss: A Multistep Diagnostic Strategy in the Italian Population

et al. 2023

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Hearing loss is the most frequent sensorineural disorder, affecting approximately 1:1000 newborns. Hereditary forms (HHL) represent 50–60% of cases, highlighting the relevance of genetic testing in deaf patients. HHL is classified as non-syndromic (NSHL—70% of cases) or syndromic (SHL—30% of cases). In this study, a multistep and integrative approach aimed at identifying the molecular cause of HHL in 102 patients, whose GJB2 analysis already showed a negative result, is described. In NSHL patients, multiplex ligation probe amplification and long-range PCR analyses of the STRC gene solved 13 cases, while whole exome sequencing (WES) identified the genetic diagnosis in 26 additional ones, with a total detection rate of 47.6%. Concerning SHL, WES detected the molecular cause in 55% of cases. Peculiar findings are represented by the identification of four subjects displaying a dual molecular diagnosis and eight affected by non-syndromic mimics, five of them presenting Usher syndrome type 2. Overall, this study provides a detailed characterisation of the genetic causes of HHL in the Italian population. Furthermore, we highlighted the frequency of Usher syndrome type 2 carriers in the Italian population to pave the way for a more effective implementation of diagnostic and follow-up strategies for this disease.

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Section: Discussionmentioning

confidence: 97%

The Enigmatic Genetic Landscape of Hereditary Hearing Loss: A Multistep Diagnostic Strategy in the Italian Population

et al. 2023

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“…It provides prognostic information on the possible progression of hearing loss, permits meaningful genetic counseling, and impacts treatment decisions [ 10 , 31 ]. The clinical features of hearing loss caused by STRC and USH2A gene mutations that are most frequent in the Russian population were presented in our previous papers [ 14 , 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…We enrolled 226 patients who were clinically diagnosed with sensorineural NSHL. Part of this cohort was previously described in three studies conducted by Markova et al and Lalayants et al that presented the phenotypes and the audiological features of hearing loss caused by mutations in the STRC , USH2A , and OTOF genes [ 14 , 15 , 16 ]. The current study is intended to provide an understanding of the mutation spectrum in non- GJB2 -related hearing loss in a cohort of Russian sensorineural NSHL patients and establish the best diagnostic algorithm.…”

Section: Introductionmentioning

confidence: 99%

Spectrum of Genes for Non-GJB2-Related Non-Syndromic Hearing Loss in the Russian Population Revealed by a Targeted Deafness Gene Panel

Shatokhina

Галеева

Степанова

et al. 2022

IJMS

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Hearing loss is one of the most genetically heterogeneous disorders known. Over 120 genes are reportedly associated with non-syndromic hearing loss (NSHL). To date, in Russia, there have been relatively few studies that apply massive parallel sequencing (MPS) methods to elucidate the genetic factors underlying non-GJB2-related hearing loss cases. The current study is intended to provide an understanding of the mutation spectrum in non-GJB2-related hearing loss in a cohort of Russian sensorineural NSHL patients and establish the best diagnostic algorithm. Genetic testing using an MPS panel, which included 33 NSHL and syndromic hearing loss (SHL) genes that might be misdiagnosed as NSHL genes, was completed on 226 sequentially accrued and unrelated patients. As a result, the molecular basis of deafness was found in 21% of the non-GJB2 NSHL cases. The total contribution pathogenic, and likely pathogenic, variants in the genes studied among all hereditary NSHL Russian patients was 12%. STRC pathogenic and likely pathogenic, variants accounted for 30% of diagnoses in GJB2-negative patients, providing the most common diagnosis. The majority of causative mutations in STRC involved large copy number variants (CNVs) (80%). Among the point mutations, the most common were c.11864G>A (p.Trp3955*) in the USH2A gene, c.2171_2174delTTTG (p.Val724Glyfs*6) in the STRC gene, and c.107A>C (p.His36Pro) and c.1001G>T (p.Gly334Val) in the SLC26A4 gene. Pathogenic variants in genes involved in SHL accounted for almost half of the cases with an established molecular genetic diagnosis, which were 10% of the total cohort of patients with non-GJB2-related hearing loss.

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“…Third, when we estimated the prevalence of DFNB16 in genetically confirmed cases (non-GJB2), DIS in DFNB16, and biallelic deletions in STRC-associated HI patients, we removed studies with probands <10, which accords with the sample size exclusion criteria mentioned. From databases and references, only Cada et al ( 2019 ) and Markova et al ( 2020 ) showed more than 10 DFNB16 sample sizes for clinical features of DFNB16. However, we rejected these studies because it was unclear whether the data presented were for all the original patients or only the cases selected after qualified audiological examination was completed.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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Background: Mutations in the STRC (MIM 606440) gene, inducing DFNB16, are considered a major cause of mild–moderate autosomal recessive non-syndromic hearing loss (ARNSHL). We conducted a systematic review and meta-analysis to determine the global prevalence and characteristics of STRC variations, important information required for genetic counseling.Methods: PubMed, Google Scholar, Medline, Embase, and Web of Science were searched for relevant articles published before January 2021.Results: The pooled prevalence of DFNB16 in GJB2-negative patients with hearing loss was 4.08% (95% CI: 0.0289–0.0573), and the proportion of STRC variants in the mild–moderate hearing loss group was 14.36%. Monoallelic mutations of STRC were 4.84% (95% CI: 0.0343–0.0680) in patients with deafness (non-GJB2) and 1.36% (95% CI: 0.0025–0.0696) in people with normal hearing. The DFNB16 prevalence in genetically confirmed patients (non-GJB2) was 11.10% (95% CI: 0.0716–0.1682). Overall pooled prevalence of deafness–infertility syndrome (DIS) was 36.75% (95% CI: 0.2122–0.5563) in DFNB16. The prevalence of biallelic deletions in STRC gene mutations was 70.85% (95% CI: 0.5824–0.8213).Conclusion: Variants in the STRC gene significantly contribute to mild–moderate hearing impairment. Moreover, biallelic deletions are a main feature of STRC mutations. Copy number variations associated with infertility should be seriously considered when investigating DFNB16.

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Clinical features of hearing loss caused by STRC gene deletions/mutations in Russian population

Cited by 13 publications

References 34 publications

The Enigmatic Genetic Landscape of Hereditary Hearing Loss: A Multistep Diagnostic Strategy in the Italian Population

The Enigmatic Genetic Landscape of Hereditary Hearing Loss: A Multistep Diagnostic Strategy in the Italian Population

Spectrum of Genes for Non-GJB2-Related Non-Syndromic Hearing Loss in the Russian Population Revealed by a Targeted Deafness Gene Panel

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

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