Data/hora: 10/06/2024 06:51:34

Provedor de dados: | 74
País: | Brazil
Título: | Phenotype-oriented NGS panels for mucopolysaccharidoses: Validation and potential use in the diagnostic flowchart
Autores: | Brusius-Facchin,Ana Carolina; Siebert,Marina; Leão,Delva; Malaga,Diana Rojas; Pasqualim,Gabriela; Trapp,Franciele; Matte,Ursula; Giugliani,Roberto; Leistner-Segal,Sandra.
Data: | 2019-01-01
Ano: | 2019
Palavras-chave: | Lysosomal storage disease; Mucopolysaccharidoses; Next generation sequencing; Target sequence; Mutation detection.
Resumo: | Abstract Mucopolysaccharidosis (MPS) are a group of rare genetic disorders caused by deficiency in the activity of specific lysosomal enzymes required for the degradation of glycosaminoglycans (GAGs). A defect in the activity of these enzymes will result in the abnormal accumulation of GAGs inside the lysosomes of most cells, inducing progressive cellular damage and multiple organ failure. DNA samples from 70 patients with biochemical diagnosis of different MPSs genotypes confirmed by Sanger sequencing were used to evaluate a Next Generation Sequencing (NGS) protocol. Eleven genes related to MPSs were divided into three different panels according to the clinical phenotype. This strategy led to the identification of several pathogenic mutations distributed across all exons of MPSs-related genes. We were able to identify 96% of all gene variants previously identified by Sanger sequencing, showing high sensitivity in detecting different types of mutations. Furthermore, new variants were not identified, representing 100% specificity of the NGS protocol. The use of this NGS approach for genotype identification in MPSs is an attractive option for diagnosis of patients. In addition, the MPS diagnosis workflow could be divided in a two-tier approach: NGS as a first-tier followed by biochemical confirmation as a second-tier.
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019000200207
Editor: | Sociedade Brasileira de Genética
Relação: | 10.1590/1678-4685-gmb-2018-0102
Formato: | text/html
Fonte: | Genetics and Molecular Biology  v.42 n.1 suppl.1 2019
Fonte: | info:eu-repo/semantics/openAccess