RESUMO

Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome, MPS VI) is an autosomal recessive disorder caused by deficiency of N-acetylgalactosamine-4-sulphatase (ARSB),which leads to the lysosomal accumulation and excretion of dermatan sulphate (DS). In this study, 13 unrelated MPS VI patients (12 Brazilian and 1 Chilean) were investigated regarding the identification of the ARSB gene mutations using PCR, SSCP and sequencing. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. Seven novel mutations were identified: D59N, L72R, Q88H, P93S, R197X, 1279delA and c.1143-8T > G. The previously reported mutations 1533del23, R315Q and 427delG were found in six, three and two alleles respectively. The other mutations already reported, S384N and G144R, were found in only one allele. In addition, three polymorphisms previously described (V358M, V376M and P397P) were detected in the patients analysed. Our findings are in agreement with the literature confirming the great genetic heterogeneity associated with MPS VI.

Assuntos

Mucopolissacaridose VI/enzimologia , Mucopolissacaridose VI/genética , Mutação , N-Acetilgalactosamina-4-Sulfatase/genética , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Condroitina Sulfatases/genética , Análise Mutacional de DNA , Éxons , Variação Genética , Humanos , Lactente , Mutação Puntual , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples , Análise de Sequência de DNA , América do Sul