Mutational spectrum in patients with dominant non-syndromic hearing loss in Austria.
Eur Arch Otorhinolaryngol
; 281(7): 3577-3586, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38400873
ABSTRACT
PURPOSE:
Hearing loss (HL) is often monogenic. The clinical importance of genetic testing in HL may further increase when gene therapy products become available. Diagnoses are, however, complicated by a high genetic and allelic heterogeneity, particularly of autosomal dominant (AD) HL. This work aimed to characterize the mutational spectrum of AD HL in Austria.METHODS:
In an ongoing prospective study, 27 consecutive index patients clinically diagnosed with non-syndromic AD HL, including 18 previously unpublished cases, were analyzed using whole-exome sequencing (WES) and gene panels. Novel variants were characterized using literature and bioinformatic means. Two additional Austrian medical centers provided AD HL mutational data obtained with in-house pipelines. Other Austrian cases of AD HL were gathered from literature.RESULTS:
The solve rate (variants graded as likely pathogenic (LP) or pathogenic (P)) within our cohort amounted to 59.26% (16/27). MYO6 variants were the most common cause. One third of LP/P variants were truncating variants in haploinsufficiency genes. Ten novel variants in HL genes were identified, including six graded as LP or P. In one cohort case and one external case, the analysis uncovered previously unrecognized syndromic presentations.CONCLUSION:
More than half of AD HL cases analyzed at our center were solved with WES. Our data demonstrate the importance of genetic testing, especially for the diagnosis of syndromic presentations, enhance the molecular knowledge of genetic HL, and support other laboratories in the interpretation of variants.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sequenciamento do Exoma
/
Mutação
Limite:
Adolescent
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Adult
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Aged
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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
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Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Eur Arch Otorhinolaryngol
Assunto da revista:
OTORRINOLARINGOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Áustria