Panel-based next-generation sequencing identifies novel mutations in Bulgarian patients with inherited retinal dystrophies.
ATP-Binding Cassette Transporters
/ genetics
Bestrophins
/ genetics
Bulgaria
Cadherin Related Proteins
Cadherins
/ genetics
DNA Copy Number Variations
Eye Proteins
/ genetics
High-Throughput Nucleotide Sequencing
Humans
Mutation
Nerve Tissue Proteins
/ genetics
Pedigree
Retinal Dystrophies
/ diagnosis
inherited retinal degeneration
molecular diagnostics
novel mutations
targeted next generation sequencing
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:
08 2022
08 2022
Historique:
revised:
07
04
2022
received:
29
11
2021
accepted:
13
05
2022
pubmed:
4
6
2022
medline:
10
8
2022
entrez:
3
6
2022
Statut:
ppublish
Résumé
Next-generation sequencing (NGS)-based method is being used broadly for genetic testing especially for clinically and genetically heterogeneous disorders, such as inherited retinal degenerations (IRDs) but still not routinely used for molecular diagnostics in Bulgaria. Consequently, the purpose of this study was to evaluate the effectiveness of a molecular diagnostic approach, based on targeted NGS for the identification of the disease-causing mutations in 16 Bulgarian patients with different IRDs. We applied a customized NGS panel, including 125 genes associated with retinal and other eye diseases to the patients with hereditary retinopathies. Systematic filtering approach coupled with copy number variation analysis and segregation study lead to the identification of 16 pathogenic and likely pathogenic variants in 12/16 (75%) of IRD patients, 2 of which novel (12.5%): ABCA4-c.668delA (p.K223Rfs18) and RР1-c.2015dupA (p.K673Efs*25). Mutations in the ABCA4, PRPH2, USH2A, BEST1, RР1, CDHR1, and RHO genes were detected reaching a diagnostic yield between 42.9% for Retinitis pigmentosa cases and 100% for macular degeneration, Usher syndrome, and cone-rod dystrophy patients. Our results confirm the usefulness of targeted NGS approach based on frequently mutated genes as a comprehensive and successful genetic diagnostic tool for IRDs with significant impact on patients counseling.
Sections du résumé
BACKGROUND
Next-generation sequencing (NGS)-based method is being used broadly for genetic testing especially for clinically and genetically heterogeneous disorders, such as inherited retinal degenerations (IRDs) but still not routinely used for molecular diagnostics in Bulgaria. Consequently, the purpose of this study was to evaluate the effectiveness of a molecular diagnostic approach, based on targeted NGS for the identification of the disease-causing mutations in 16 Bulgarian patients with different IRDs.
METHODS
We applied a customized NGS panel, including 125 genes associated with retinal and other eye diseases to the patients with hereditary retinopathies.
RESULTS
Systematic filtering approach coupled with copy number variation analysis and segregation study lead to the identification of 16 pathogenic and likely pathogenic variants in 12/16 (75%) of IRD patients, 2 of which novel (12.5%): ABCA4-c.668delA (p.K223Rfs18) and RР1-c.2015dupA (p.K673Efs*25). Mutations in the ABCA4, PRPH2, USH2A, BEST1, RР1, CDHR1, and RHO genes were detected reaching a diagnostic yield between 42.9% for Retinitis pigmentosa cases and 100% for macular degeneration, Usher syndrome, and cone-rod dystrophy patients.
CONCLUSION
Our results confirm the usefulness of targeted NGS approach based on frequently mutated genes as a comprehensive and successful genetic diagnostic tool for IRDs with significant impact on patients counseling.
Identifiants
pubmed: 35656873
doi: 10.1002/mgg3.1997
pmc: PMC9356554
doi:
Substances chimiques
ABCA4 protein, human
0
ATP-Binding Cassette Transporters
0
BEST1 protein, human
0
Bestrophins
0
CDHR1 protein, human
0
Cadherin Related Proteins
0
Cadherins
0
Eye Proteins
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1997Informations de copyright
© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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