Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss.
Sci Rep
; 11(1): 22488, 2021 11 18.
Article
em En
| MEDLINE
| ID: mdl-34795337
The genetic heterogeneity of sensorineural hearing loss (SNHL) is a major hurdle to the detection of disease-causing variants. We aimed to identify underlying causal genes associated with mid-frequency hearing loss (HL), which contributes to less than about 1% of SNHL cases, by whole exome sequencing (WES). Thirty families segregating mid-frequency SNHL, in whom biallelic GJB2 mutations had been previously excluded, were selected from among 851 families in our DNA repository of SNHL. DNA samples from the probands were subjected to WES analysis and searched for candidate variants associated with SNHL. We were able to identify the genetic aetiology in six probands (20%). In total, we found three pathogenic and three likely pathogenic variants in four genes (COL4A5, OTOGL, TECTA, TMPRSS3). One more proband was a compound heterozygote for a pathogenic variant and a variant of uncertain significance (VUS) in MYO15A gene. To date, MYO15A and TMPRSS3 have not yet been described in association with mid-frequency SNHL. In eight additional probands, eight candidate VUS variants were detected in five genes (DIAPH1, MYO7A, TECTA, TMC1, TSPEAR). Seven of these 16 variants have not yet been published or mentioned in the available databases. The most prevalent gene was TECTA, identified in 23% of all tested families. Furthermore, we confirmed the hypothesis that a substantive portion of cases with this conspicuous audiogram shape is a consequence of a genetic disorder.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Marcadores Genéticos
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Perda Auditiva Neurossensorial
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Adult
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Eslováquia
País de publicação:
Reino Unido