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IGMJM, Unidade de Enzimologia- Porto and IBMC, Unilipe- Universidade do Porto Resumo disponível em: J Inherit Metab Dis. 2004;27 Supl 1:184 (363P) Mucopolysaccharidosis type VI (MPS VI, OMIM 253200) is a rare autosomal recessive disorder characterized by the deficient activity of arylsulfatase B (ARSB, EC 3.1.6.12). In Portugal, the birth prevalence of the rare MPS VI is 0.42/100000. With the emerging availability of promising enzyme replacement therapy for this disease, mutation analysis becomes an important tool not only for the genetic counselling of individuals at risk, but also in the prognosis of the disease and identification of cases which might benefit of an early therapeutic intervention. In this work we present the preliminary results obtained through mutation analysis of 12 Portuguese patients. This study involved PCR amplification and direct automated sequencing analysis of exons and intron boundaries. The identification of seven mutations is reported: two recently described deletions, three missense mutations (two of them new), one novel nonsense mutation and also one new splicing mutation. Additionally, two previously described point mutations were detected in the form of a complex allele. Seven patients were homozygous for various mutations, while the remaining five were compound heterozygotes. Interestingly, three mutations seem to have an increased frequency in the Portuguese sample studied jointly c.1533del23 (Petry et al.,2003), c.427delG (Karageorgos et al.,2004) and R315Q (Villani et al.,1999) represent 58% of the patients alleles. In some of the cases Western blot analysis was also carried out. The impact of the various mutations at the protein level and the resulting phenotypic implications are discussed. |
