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

• Autor(a) principal: Málaga, Diana Elizabeth Rojas
• Data de Publicação: 2019
• Outros Autores: Facchin, Ana Carolina Brusius, Siebert, Marina, Pasqualim, Gabriela, Pereira, Maria Luiza Saraiva, Souza, Carolina Fischinger Moura de, Schwartz, Ida Vanessa Doederlein, Matte, Ursula da Silveira, Giugliani, Roberto
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/199713
• topic: Doenças por armazenamento dos lisossomos; Patologia molecular; Ion Torrent; Molecular diagnostics; Next-generation sequencing; Lysosomal storage disorders

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.