Molecular analysis of mucopolysaccharidosis type VI in Poland, Belarus, Lithuania and Estonia

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• 作者：Agnieszka Jurecka^a ; ^b ; ^{ajurecka@gmail.com} ; Ewa Piotrowska^a ; Loreta Cimbalistiene^c ; Nina Gusina^d ; Agnieszka Sobczyń ; ska^e ; Barbara Czartoryska^f ; Kamila Czerska^e ; Katrin Õ ; unap^g ; ^h ; Grzegorz Wę ; grzyn^a ; Anna Tylki-Szymań ; ska^b ; ^{a.tylki@czd.pl}
• 关键词：ARSB ; Genotype&ndash ; phenotype analysis ; Maroteaux&ndash ; Lamy syndrome ; Mucopolysaccharidosis type VI
• 刊名：Molecular Genetics and Metabolism
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：105
• 期：2
• 页码：237-243
• 全文大小：367 K

文摘

Mucopolysaccharidosis VI (MPS VI) is a rare autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-4-sulfatase (ARSB). Over 130 ARSB gene mutations have been identified thus far and most mutations are unique to individual families. We aimed to analyze the spectrum of mutations in the ARSB gene responsible for the disorder in Poland, Belarus and Baltic States. Twenty one families with MPS VI patients, in whom diagnosis was confirmed biochemically and enzymatically, were studied. Direct sequencing of patient genomic DNA was used to identify ARSB mutations. In total, fourteen different disease-causing mutations were found. Three novel mutations included insertion c.375_376insT, a missense mutation c.499G>A (p.G167R) and deletion/insertion c.750_754delinsCCTGAAGTCAAG. We also report 11 previously described mutations (p.A33V, p.W57C, p.Q88X, p.T92K, p.Q97X, p.R152W, p.R160Q, p.R160X, p.Y210C, p.Y266S, p.G302R). The mutation p.R152W was present at a high prevalence of 50 % (21/42) the mutated alleles in this group of patients. High prevalence of p.R152W mutation in Poland, Belarus and Baltic States indicates a possible founder effect and suggests that screening for this mutation may be appropriate in MPS VI patients from this region. Our study has also provided evidence to support genotype-phenotype correlation.