Panel-based next-generation sequencing identifies novel mutations in Bulgarian patients with inherited retinal dystrophies.

Autor: Kamenarova K; Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.; Laboratory of Genomic Diagnostics, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria., Mihova K; Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.; Laboratory of Genomic Diagnostics, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria., Veleva N; Department of Ophthalmology, University Hospital 'Alexandrovska', Medical University of Sofia, Sofia, Bulgaria., Mermeklieva E; Clinic of Ophthalmology, University Hospital 'Lozenetz', Medical Faculty, Sofia University 'St. Kliment Ohridski', Sofia, Bulgaria., Mihaylova B; Clinic 'Vision', Sofia, Bulgaria., Dimitrova G; Department of Ophthalmology, University Hospital 'Alexandrovska', Medical University of Sofia, Sofia, Bulgaria., Oscar A; Department of Ophthalmology, University Hospital 'Alexandrovska', Medical University of Sofia, Sofia, Bulgaria., Shandurkov I; Clinic 'Vision', Sofia, Bulgaria., Cherninkova S; Department of Neurology, University hospital 'Alexandrovska', Medical University of Sofia, Sofia, Bulgaria., Kaneva R; Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.; Laboratory of Genomic Diagnostics, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2022 Aug; Vol. 10 (8), pp. e1997. Date of Electronic Publication: 2022 Jun 03.
DOI: 10.1002/mgg3.1997
Abstrakt: 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.
(© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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