| Autor: |
Oziębło, D., Leja, M. L., Gan, N., Bałdyga, N., Sarosiak, A., Skarzynski, H., Ołdak, M. |
| Předmět: |
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| Zdroj: |
Journal of Hearing Science; Sep2024, Vol. 14 Issue 3, p94-94, 1/3p |
| Abstrakt: |
Introduction: Autosomal dominant hearing loss (ADHL) is the second most common form of inherited HL with an onset usually after the first decade of life. It affects mainly high frequencies and progresses over time. Autosomal-dominant genes are responsible for about 20% of cases of hereditary non-syndromic deafness, with 63 different genes identified to date. Material and methods: In this study, 105 families with a vertical inheritance pattern of hearing impairment were recruited. Genomic DNA was isolated from peripheral blood samples or buccal swabs of available family members. In all probands targeted next-generation sequencing (NGS) using a targeted multi-gene panel (237 genes) was performed. In 6 largest unsolved families linkage analysis and whole genome sequencing (WGS) were performed. Presence of the selected probably pathogenic variants and their segregation with HL within the family were confirmed by standard Sanger sequencing. Results: Genetic cause of ADHL was identified in 43.8% (46/105) of the examined families. Among the 46 identified HL variants only 26% (12/46) have been previously reported and the remaining 74% are novel (34/46). We identified missense variants (27/46; 58.7%), splice site variant (9/46; 19.5%), stop-gain variants (5/46; 10.9%) as well as frameshift variants (5/46; 10.9%). Among the most common causative genes were MYO6 (n = 8), TBC1D24 (n = 5), KCNQ4 (n = 4), GSDME (n = 4), POU4F3 (n = 4) and WFS1 (n = 4). Pathogenic variants causative of HL in the NLRP3, LMX1A, FGFR3, CD164, GRHL2, TMC1, COCH, ATP2B2 and CEACAM16 genes were detected in single families. Implementation of linkage analysis and WGS resulted in the identification of the non-coding variants in the EYA4 and ATP11A genes and two novel candidate genes. Conclusions: Our custom multigene panel has demonstrated good diagnostic performance. Considering frequent identification of novel genetic variants it is necessary to perform thorough clinical examination and variant segregation analysis with ADHL in all available family members. The use of linkage analysis and WGS increases the detection rate of causative variants, especially located in the non-coding regions, and provides the opportunity to identify novel genes. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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