Spectrum of Genes for Non-GJB2-Related Non-Syndromic Hearing Loss in the Russian Population Revealed by a Targeted Deafness Gene Panel.
| Title: | Spectrum of Genes for Non-GJB2-Related Non-Syndromic Hearing Loss in the Russian Population Revealed by a Targeted Deafness Gene Panel. |
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| Authors: | Shatokhina O; Federal State Budgetary Institution 'Research Centre For Medical Genetics', 115478 Moscow, Russia.; Galeeva N; Federal State Budgetary Institution 'Research Centre For Medical Genetics', 115478 Moscow, Russia.; Stepanova A; Federal State Budgetary Institution 'Research Centre For Medical Genetics', 115478 Moscow, Russia.; Markova T; Federal State Budgetary Institution of Science 'National Research Centre for Audiology and Hearing Rehabilitation', 117513 Moscow, Russia.; Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education', 125993 Moscow, Russia.; Lalayants M; Federal State Budgetary Institution of Science 'National Research Centre for Audiology and Hearing Rehabilitation', 117513 Moscow, Russia.; Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education', 125993 Moscow, Russia.; Alekseeva N; Federal State Budgetary Institution of Science 'National Research Centre for Audiology and Hearing Rehabilitation', 117513 Moscow, Russia.; Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education', 125993 Moscow, Russia.; Tavarkiladze G; Federal State Budgetary Institution of Science 'National Research Centre for Audiology and Hearing Rehabilitation', 117513 Moscow, Russia.; Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education', 125993 Moscow, Russia.; Markova T; Federal State Budgetary Institution 'Research Centre For Medical Genetics', 115478 Moscow, Russia.; Bessonova L; Federal State Budgetary Institution 'Research Centre For Medical Genetics', 115478 Moscow, Russia.; Petukhova M; Federal State Budgetary Institution 'Research Centre For Medical Genetics', 115478 Moscow, Russia.; Guseva D; Federal State Budgetary Institution 'Research Centre For Medical Genetics', 115478 Moscow, Russia.; Anisimova I; Federal State Budgetary Institution 'Research Centre For Medical Genetics', 115478 Moscow, Russia.; Polyakov A; Federal State Budgetary Institution 'Research Centre For Medical Genetics', 115478 Moscow, Russia.; Ryzhkova O; Federal State Budgetary Institution 'Research Centre For Medical Genetics', 115478 Moscow, Russia.; Bliznetz E; Federal State Budgetary Institution 'Research Centre For Medical Genetics', 115478 Moscow, Russia. |
| Source: | International journal of molecular sciences [Int J Mol Sci] 2022 Dec 12; Vol. 23 (24). Date of Electronic Publication: 2022 Dec 12. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, [2000- |
| MeSH Terms: | Deafness*/genetics ; Hearing Loss*/genetics ; Hearing Loss, Sensorineural*/genetics; Connexins/genetics ; Connexin 26/genetics ; Intercellular Signaling Peptides and Proteins/genetics ; Humans ; Mutation |
| Abstract: | 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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| Contributed Indexing: | Keywords: MPS; hearing loss; non-GJB2 related; non-syndromic; panel sequencing |
| Substance Nomenclature: | 0 (Connexins); 127120-53-0 (Connexin 26); 0 (STRC protein, human); 0 (Intercellular Signaling Peptides and Proteins) |
| SCR Disease Name: | Nonsyndromic Deafness |
| Entry Date(s): | Date Created: 20221223 Date Completed: 20221226 Latest Revision: 20230308 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9779600 |
| DOI: | 10.3390/ijms232415748 |
| PMID: | 36555390 |
| Database: | MEDLINE |
Journal Article