N-acetylgalactosamine-4-sulfatase: identification of four new mutations within the conserved sulfatase region causing mucopolysaccharidosis type VI.

Mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome) is the lysosomal storage disorder resulting from the deficient activity of N-acetylgalactosamine-4-sulfatase (arylsulfatase B; ASB). MPS VI has been described in man, cats and rats, and several mutations in the ASB gene have been identified in human patients and the animal models. Notably, ASB belongs to a family of sulfatases which are highly conserved, suggesting that they are related evolutionarily and functionally. In this manuscript, four new mutations causing MPS VI are described within the human ASB gene. Each of these mutations occurred in or near the hexapeptide 144GKWHLG149, one of the most highly conserved 'sulfatase' regions. In fact, three of the mutations occurred within the same codon, W146. Thus, these results provide new insights into the molecular lesions causing MPS VI and highlight the importance of this conserved sulfatase region.