title: Analysis of five mutations in 20 mucopolysaccharidois type 1 patients: high prevalence of the W402X mutation. Mutations in brief no. 121. Online.
abstract: Mucopolysaccharidosis type 1 is a lysosomal storage disease due to a L-Iduroniase deficiency. Three main phenotypes have been reported: Hurler (severe), Scheie (mild) and Hurler/Scheie (intermediate). High prevalence of mutations W402X and Q70X has been described. We studied these two mutations in 20 unrelated MPSI Spanish patients. In addition we have also analysed the P533R mutation because of its frequency in the close Mediterranean country Italy and mutations R89Q and 678-7g->a because of its prevalence in European Scheie syndrome. We found that 60% (24/40) mutated alleles carried the W402X mutation, 40% of them in homozygosity. Such a high prevalence of this mutation has not been described so far. Patients who carry this mutation in both alleles or in combination with Q70X and P533R have a severe phenotyoe. 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 phenotype. The P533R mutation accounts for 10% (4/40) of the alleles.  One Hurler phenotype patient was homozygous for this mutation. No patient presented the R89Q or 678-7g->a mutations. In conclusion, screening of Spanish patients for mutations W402X, Q70X and P533R allowed identification of 80% of the mutant alleles and genotyping of 70% of patients.
authors.affiliation: Institut de Bioquímica Clínica, Corporació Sanitària, Edifici Helios III, C/Mejía Lequerica, s/n, 08028 Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Gort
authors.forename: A
authors.initials: A
authors.lastname: Chabás
authors.forename: M J
authors.initials: MJ
authors.lastname: Coll
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008059:Mucopolysaccharidosis I / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D013030:Spain / Q000453:epidemiology; D014364:Tryptophan / Q000235:genetics*
chemical_list: D014364:Tryptophan