Identification of the molecular defects in Spanish and Argentinian mucopolysaccharidosis VI (Maroteaux–Lamy syndrome) patients, including 9 novel mutations

详细信息	查看全文 | 推荐本文 |

• 作者：Elena Garrido ; Amparo Chabá ; s ; Maria Josep Coll ; Mariana Blanco ; Carmen Domí ; nguez ; Daniel Grinberg ; Lluï ; sa Vilageliu ; Bru Corm
• 关键词：Maroteaux– ; Lamy syndrome ; Mucopolysaccharidosis VI ; MPS VI ; N-Acetylgalactosamine-4-sulfatase ; Arylsulfatase B ; ARSB gene ; Mutational analysis ; Haplotype analysis
• 刊名：Molecular Genetics and Metabolism
• 出版年：2007
• 期刊代码：175_10967192
• 类别：bio
• 出版时间：September-October 2007
• 卷：92
• 期：1-2
• 页码：122-130
• 文件大小：467 K

摘要

Maroteaux–Lamy syndrome, or mucopolysaccharidosis VI (MPS VI), is an autosomal recessive lysosomal storage disorder caused by a deficiency of N-acetylgalactosamine-4-sulfatase or arylsulfatase B (ARSB). We aimed to analyze the spectrum of mutations responsible for the disorder in Spanish and Argentinian patients, not previously studied. We identified all the ARSB mutant alleles, nine of them novel, in 12 Spanish and 4 Argentinian patients. The new changes were as follows: six missense mutations: c.245T>G [p.L82R], c.413A>G [p.Y138C], c.719C>T [p.S240F], c.922G>A [p.G308R], c.1340G>T [p.C447F] and c.1415T>C [p.L472P]; one nonsense mutation: c.966G>A [p.W322X]; and two intronic changes involving splice sites: c.1142+2T>A, in the donor splice site of intron 5, which promotes skipping of exon 5, and c.1143−1G>C, which disrupts the acceptor site of intron 5, resulting in skipping of exon 6. We also report 10 previously described mutations as well as several non-pathogenic polymorphisms. Haplotype analysis indicated a common origin for most of the mutations found more than once. Most of the patients were compound heterozygotes, whereas only four of them were homozygous. These observations confirm the broad allelic heterogeneity of the disease, with 19 different mutations in 16 patients. However, the two most frequent mutations, c.1143−1G>C and c.1143−8T>G, present in both populations, accounted for one-third of the mutant alleles in this group of patients.