ANALYSIS OF 5 MUTATIONS IN 20 MUCOPOLYSACCHARIDOSIS TYPE-I PATIENTS -HIGH PREVALENCE OF THE W402X-MUTATION

Mucopolysaccharidosis type I is a lysosomal storage disease due to a L -Iduronidase deficiency. Three main phenotypes have been reported: Hur ler (severe), Scheie (mild) and Hurler/Scheie (intermediate). High pre valence of mutations W402X and Q70X has been described. We studied the se two mutations in 20 unrelated MPS I Spanish patients. In addition, we have also analysed the P533R mutation because of its frequency in t he close Mediterranean country Italy and mutations R89Q and 678-7g-a b ecause of its prevalence in European Scheie syndrome. We found that 60 % (24/40) mutated alleles carried the W402X mutation, 40% of them in h omozygosity. Such a high prevalence of this mutation has not been desc ribed so far. Patients who carry this mutation in both alleles or in c ombination with Q70X and P533R have a severe phenotype. Mutation Q70X was found in 10% (4/40) of the alleles, two of them in heterozygosity with W402X. Patient with Q70X/Q70X genotype had a severe Hurler phenot ype. The P533R mutation accounts also for 10% (4/40) of the alleles. O ne Hurler phenotype patient was homozygous for this mutation. No patie nt presented the R89Q or 678-7g-a mutations.