Genetic analysis of mucopolysaccharidosis type VI in Taiwanese patients

Abstract

Background Mucopolysaccharidosis type VI (MPS VI; Maroteaux–Lamy syndrome) is an autosomal recessive lysosomal storage disease induced by a deficiency of the enzyme N-acetylgalactosamine-4-sulfatase (arylsulfatase B, ARSB). The deficiency of ARSB leads to an accumulation of dermatan sulfate (DS) in lysosomes and gross excretion in the urine. The prevalence of these mutations in Asian MPS VI patients has not yet been thoroughly investigated. We studied the ARSB gene profile of 9 Taiwanese MPS VI patients. Methods To validate the patients' type of MPS, urine mucopolysaccharide was defined by 2-dimensional electrophoresis and leukocyte ARSB activity was determined by fluorogenic assay. Direct sequencing was used to identify any mutation in the patients' ARSB gene. Results Abnormal excretion of DS and low leukocyte ARSB activity was observed in the urine samples of all 9 patients studied. A total of 8 mutations within the ARSB gene were revealed by molecular analysis. Four mutations, c.574T > C (p.Cys192Arg) and c.943C > T (p.Arg315Stop) mutations had been observed in other populations and c.716A > G (p.Gln239Arg) and c.1197C > G (p.Phe399Leu) were previously reported by our group. The other 4 mutations c.395T > C (p.Leu132Pro), c.908G > A (p.Gly303Glu), c.1228 C > A (p.His430Asn) and c.1394C > G (p.Ser465X), had not been reported before. The c.1197C > G (p.Phe399Leu) and c.395T > C (p.Leu132Pro) mutations were the most common missense mutation in the patients studied (8 in 18 mutant alleles). According to statistical data, the incidence of MPS VI in Taiwan is approximately 1 in 833,000 in live birth. Conclusion The ARSB gene mutation profile in Taiwanese MPS VI patients may be different from MPS VI patients from other countries.