title: Molecular analysis of mucopolysaccharidosis type VI in Poland, Belarus, Lithuania and Estonia.
abstract: 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.
authors: Department of Molecular Biology, University of Gdańsk, Gdańsk, Poland. ajurecka@gmail.com
authors: Agnieszka
authors: A
authors: Jurecka
authors: Ewa
authors: E
authors: Piotrowska
authors: Loreta
authors: L
authors: Cimbalistiene
authors: Nina
authors: N
authors: Gusina
authors: Agnieszka
authors: A
authors: Sobczyńska
authors: Barbara
authors: B
authors: Czartoryska
authors: Kamila
authors: K
authors: Czerska
authors: Katrin
authors: K
authors: Õunap
authors: Grzegorz
authors: G
authors: Węgrzyn
authors: Anna
authors: A
authors: Tylki-Szymańska
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004957:Estonia / Q000453:epidemiology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008097:Lithuania / Q000453:epidemiology; D008297:Male; D009087:Mucopolysaccharidosis VI / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000235:genetics* / Q000378:metabolism*; D057089:Pathology, Molecular; D011044:Poland / Q000453:epidemiology; D002094:Republic of Belarus / Q000453:epidemiology; D017422:Sequence Analysis, DNA
chemical_list: D020051:N-Acetylgalactosamine-4-Sulfatase