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 Rojas
• Data de Publicação: 2019
• Outros Autores: Brusius-Facchin,Ana Carolina, Siebert,Marina, Pasqualim,Gabriela, Saraiva-Pereira,Maria Luiza, Souza,Carolina F.M de, Schwartz,Ida V.D., Matte,Ursula, Giugliani,Roberto
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Genetics and Molecular Biology
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019000200197
• topic: Ion Torrent; molecular diagnostics; next-generation sequencing; lysosomal storage disorders; validation

Abstract 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.