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.
Highlights
Mucopolysaccharidoses (MPSs) are a group of rare genetic disorders caused by deficiency in the activity of specific lysosomal enzymes required for the degradation of glycosaminoglycans (GAGs)
We were able to identify 98% of all variants previously identified by Sanger method, 96% in Panel 1, 100% in Panel 2, and 100% in Panel 3, showing a high sensitivity in detecting different types of mutations using this approach (Table 2)
MPSs are genetic metabolic diseases that can be caused by mutations in several distinct genes, each one coding for a specific enzyme in the GAG degradation pathway
Summary
Mucopolysaccharidoses (MPSs) 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 any of the 11 enzymes responsible for the stepwise degradation of GAGs will result in their abnormal accumulation inside the lysosomes of most cells, inducing progressive cellular damage and multiple organ failure, with consequent reduction of the quality of life and life expectancy (Neufeld and Muenzer, 2001). MPS disorders are inherited in an autosomal recessive manner and affect males and females . Ception is MPS II, an X-linked recessive disorder that primarily affects males, but due to autosomal X-chromosomal translocation and non-random X-chromosome inactivation, rare female patients with MPS II have been reported (Neufeld and Muenzer, 2001). In addition to the symptomatic manifestations, patients with severe forms of MPS
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
