Molecular analysis of 30 mucopolysaccharidosis type I patients: evaluation of the mutational spectrum in Italian population and identification of 13 novel mutations
Mucopolysaccharidosis type I (MPS‐I orMPS1) is an autosomal recessive condition characterized by a broad range of clinical symptoms. Molecular diagnosis of MPS‐I is important for analyzing genotype‐phenotype correlation and for selecting patients for innovative therapies. In this study we analyzed 30 Italian MPS‐I patients with different phenotypes (20 severe, 6 intermediate, 4 mild) in an attempt to recognize the mutational spectrum in our population and to identify major DNA alterations specific to our country. We identified 93% of mutated alleles (56 out of 60) with the reconstruction of the complete genotype in 26 patients out of 30. Twenty‐three different mutations were found, 13 of which are novel while the remaining 10 have been already described. Among the novel mutations we found 5 non conservative missense mutations (A160D, E178K, P183R, G197D, D349Y), one nonsense mutation (C53X), 6 deletions (468‐470del3, 486‐491del6, 755‐759del5, 1251delC, 1839‐1867del29, 1902‐1903del2), and one splice site mutation (IVS11+5G>A). No common mutation for MPS‐I is present in our country. Frequently (40% of the alleles), mutations were found in just one or two patients. However, Q70X, P533R, G51D, and W402X mutations were present in several patients (15%, 13.3%, 13.3%, and 11.6% of the alleles respectively) suggesting a Mediterranean origin of the P533R and G51D mutations. In most cases the patients' genotypes were unique combinations of mutations. The great heterogeneity found in our MPS‐I population hampers mutation detection and hinders the genotype‐phenotype correlation.