Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive inborn error of metabolism caused by mutations in the arylsulfatase B gene (ARSB) and consequent deficient activity of ARSB, a lysosomal enzyme. We present here the results of a study undertaken to identify the mutations in ARSB in MPS VI patients in India. Around 160 ARSB mutations, of which just 4 are from India, have been reported in the literature. Our study covered nine MPS VI patients from eight families. Both familial mutations were found in seven families, and only one mutation was found in one family. Seven mutations were found - four novel (p.G38_G40del3, p.C91R, p.L98R and p.R315P), two previously reported from India (p.D53N and p.W450C), and one reported from outside India (p.R160Q). One mutation, p.W450C, was present in two families, and the other six mutations were present in one family each. Analysis of the molecular structure of the enzyme revealed that most of these mutations either cause loss of an active site residue or destabilize the structure of the enzyme. The only previous study on mutations in ARSB in Indian MPS VI patients, by Kantaputra et al. 2014 [1], reported four novel mutations of which two (p.D53N and p.W450C) were found in our study as well. Till date, nine mutations have been reported from India, through our study and the Kantaputra study. Eight out of these nine mutations have been found only in India. This suggests that the population studied by us might have its own typical set of mutations, with other populations equally likely to have their own set of mutations.
Keywords: ARSB, arylsulfatase B; Active site; Arylsulfatase B (ARSB); ERT, enzyme replacement therapy; GAG, glycosaminoglycan; GALNS, N-acetyl galactosamine 6-sulfatase; HGMD, Human Gene Mutation Database; HSCT, hematopoietic stem cell transplantation; Inborn error of metabolism (IEM); India; LSD, lysosomal storage disorder; Lysosomal enzyme; Lysosomal storage disorder (LSD); MPS, mucopolysaccharidosis; Maroteaux–Lamy syndrome; Mucopolysaccharidosis VI (MPS VI); Mutations; PCT, pharmacological chaperone therapy; VUS, variants of unknown significance.