Custom Next-Generation Sequencing Identifies Novel Mutations Expanding the Molecular and clinical spectrum of isolated Hearing Impairment or along with defects of the retina, the thyroid, and the kidneys.
Pendred syndrome
Usher syndrome
hearing impairment
high-throughput targeted sequencing
renal tubular acidosis
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
16
12
2021
received:
21
07
2021
accepted:
28
12
2021
pubmed:
9
1
2022
medline:
30
4
2022
entrez:
8
1
2022
Statut:
ppublish
Résumé
In the Tunisian population, the molecular analysis of hearing impairment remains based on conventional approaches, which makes the task laborious and enormously expensive. Exploration of the etiology of Hearing Impairment and the early diagnosis of causal mutations by next-generation sequencing help significantly alleviate social and economic problems. We elaborated a custom SureSelect We report eight pathogenic variants, four of which are novel in patients with isolated hearing impairment, hearing impairment, and renal tubular acidosis, Usher syndrome and Pendred syndrome. Functional studies using molecular modeling showed the severe impact of the novel missense mutations on the concerned proteins. Basically, we identified mutations in nuclear as well as mitochondrial genes in a Tunisian family with isolated hearing impairment, which explains definitely the phenotype detected since 2006. Our results expanded the mutation spectrum and genotype-phenotype correlation of isolated and syndromic hearing loss and also emphasized the importance of combining both targeted next-generation sequencing and detailed clinical evaluation to elaborate a more accurate diagnosis for hearing impairment and related phenotypes especially in North African populations.
Sections du résumé
BACKGROUND
In the Tunisian population, the molecular analysis of hearing impairment remains based on conventional approaches, which makes the task laborious and enormously expensive. Exploration of the etiology of Hearing Impairment and the early diagnosis of causal mutations by next-generation sequencing help significantly alleviate social and economic problems.
METHODS
We elaborated a custom SureSelect
RESULTS
We report eight pathogenic variants, four of which are novel in patients with isolated hearing impairment, hearing impairment, and renal tubular acidosis, Usher syndrome and Pendred syndrome. Functional studies using molecular modeling showed the severe impact of the novel missense mutations on the concerned proteins. Basically, we identified mutations in nuclear as well as mitochondrial genes in a Tunisian family with isolated hearing impairment, which explains definitely the phenotype detected since 2006.
CONCLUSION
Our results expanded the mutation spectrum and genotype-phenotype correlation of isolated and syndromic hearing loss and also emphasized the importance of combining both targeted next-generation sequencing and detailed clinical evaluation to elaborate a more accurate diagnosis for hearing impairment and related phenotypes especially in North African populations.
Identifiants
pubmed: 34997822
doi: 10.1002/mgg3.1868
pmc: PMC8830811
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1868Informations de copyright
© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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