Sensitivity, advantages, limitations, and clinical utility of targeted next-generation sequencing panels for the diagnosis of selected lysosomal storage disorders.

Autor: Málaga DR; Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil., Brusius-Facchin AC; Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil., Siebert M; Experimental Research Center, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil., Pasqualim G; Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Experimental Research Center, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil.; Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil., Saraiva-Pereira ML; Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil.; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Souza CFM; Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil., Schwartz IVD; Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil.; Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Matte U; Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Experimental Research Center, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil.; Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Giugliani R; Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil.; Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Jazyk: angličtina
Zdroj: Genetics and molecular biology [Genet Mol Biol] 2019; Vol. 42 (1 suppl 1), pp. 197-206. Date of Electronic Publication: 2019 Apr 11.
DOI: 10.1590/1678-4685-GMB-2018-0092
Abstrakt: Lysosomal storage disorders (LSDs) constitute a heterogeneous group of approximately 50 genetic disorders. LSDs diagnosis is challenging due to variability in phenotype penetrance, similar clinical manifestations, and a high allelic heterogeneity. A powerful tool for the diagnosis of the disease could reduce the "diagnostic odyssey" for affected families, leading to an appropriate genetic counseling and a better outcome for current therapies, since enzyme replacement therapies have been approved in Brazil for Gaucher, Fabry, and Pompe diseases, and are under development for Niemann-Pick Type B. However, application of next-generation sequencing (NGS) technology in the clinical diagnostic setting requires a previous validation phase. Here, we assessed the application of this technology as a fast, accurate, and cost-effective method to determine genetic diagnosis in selected LSDs. We have designed two panels for testing simultaneously 11 genes known to harbor casual mutations of LSDs. A cohort of 58 patients was used to validate those two panels, and the clinical utility of these gene panels was tested in four novel cases. We report the assessment of a NGS approach as a new tool in the diagnosis of LSDs in our service.
Databáze: MEDLINE
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