Molecular analysis of mucopolysaccharidoses: identification and characterization of pathogenic mutations in Indian population

Abstract

Background Mucopolysaccharidosis (MPS) are a group of rare inherited metabolic disorders which are caused due to the deficiency of a specific lysosomal enzyme involved in the catabolism of glycosaminoglycans. These disorders show a wide clinical spectrum ranging from severe, intermediate and mild phenotypes. Most of them show overlapping clinical features such as corneal clouding, coarse facies, hepatosplenomegaly, skeletal dysplasia, short stature, dysostosis multiplex, joint stiffness, joint contractures, cardiovascular and respiratory difficulties. Certain MPS disorders also show impaired neurological functions leading to mental retardation. They are inherited as an autosomal recessive with exception of MPS II, which is X-linked recessive disorder. They exhibit clinical, genetic as well as molecular heterogeneity. To date more than 200 mutations in IDUA, ~ 500 in IDS, ~ 200 in GALNS and ~ 200 in ARSB have been reported worldwide. The mutation spectrum of MPS disorders in Indian population is not characterized and established yet. This study was done to establish mutation spectrum in the Indian population that can be useful for the design of cost-effective strategies towards the molecular diagnosis of MPS disorders.