Genetic analysis of mucopolysaccharidosis type VI in Taiwanese patients.
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.


CONCLUSIONS
The ARSB gene mutation profile in Taiwanese MPS VI patients may be different from MPS VI patients from other countries.
Lin
Wei-De
WD
Department of Medical Research, China Medical University Hospital, 2 Yuh Der Road, Taichung, Taiwan.
Lin
Shuan-Pei
SP
Wang
Chung-Hsing
CH
Hwu
Wuh-Liang
WL
Chuang
Chih-Kuang
CK
Lin
Shio-Jean
SJ
Tsai
Yushin
Y
Chen
Chih-Ping
CP
Tsai
Fuu-Jen
FJ
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D009087:Mucopolysaccharidosis VI / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D013624:Taiwan