BETA-GLUCURONIDASE P408S, P415L MUTATIONS - EVIDENCE THAT BOTH MUTATIONS COMBINE TO PRODUCE AN MPS-VII ALLELE IN CERTAIN MEXICAN PATIENTS

Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is an autosomal recessively inherited lysosomal storage disease caused by a deficienc y in beta-glucuronidase. We identified and studied a novel allele cont aining two C-to-T transitions resulting in P408S and P415L alterations , which is present in homozygous state in one Mexican patient and in h eterozygous state in another. None of the previous reports describing mutations in the MPS VII gene include Mexican patients. Expression of either of the mutations individually showed only modest effects on the properties of the enzyme. However, expression of the doubly mutant al lele resulted in markedly reduced activity and rapid degradation in an early biosynthetic compartment.