Spectrum of Genes for Non-<i>GJB2</i>-Related Non-Syndromic Hearing Loss in the Russian Population Revealed by a Targeted Deafness Gene Panel
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...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/24/15748 |
| Summary: | 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-<i>GJB2</i>-related hearing loss cases. The current study is intended to provide an understanding of the mutation spectrum in non-<i>GJB2</i>-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-<i>GJB2</i> NSHL cases. The total contribution pathogenic, and likely pathogenic, variants in the genes studied among all hereditary NSHL Russian patients was 12%. <i>STRC</i> pathogenic and likely pathogenic, variants accounted for 30% of diagnoses in <i>GJB2</i>-negative patients, providing the most common diagnosis. The majority of causative mutations in <i>STRC</i> involved large copy number variants (CNVs) (80%). Among the point mutations, the most common were c.11864G>A (p.Trp3955*) in the <i>USH2A</i> gene, c.2171_2174delTTTG (p.Val724Glyfs*6) in the <i>STRC</i> gene, and c.107A>C (p.His36Pro) and c.1001G>T (p.Gly334Val) in the <i>SLC26A4</i> 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-<i>GJB2</i>-related hearing loss. |
|---|---|
| ISSN: | 1661-6596 1422-0067 |