Mutations c.459+1G>A and p.P426L in the ARSA gene: prevalence in metachromatic leukodystrophy patients from European countries.

Abstract

In this multicentre study, we examined the prevalence of two mutations in the arylsulfatase A (ARSA) gene, i.e., c.459+1G>A and p.P426L, in 384 unrelated European patients presenting with different types of metachromatic leukodystrophy (MLD). In total, c.459+1G>A was found 194 times among the 768 investigated ARSA alleles (25%), whereas p.P426L was identified 143 times (18.6%). Thus, these two mutations accounted for 43.8% of investigated MLD alleles. Mutation c.459+1G>A was most frequent in late-infantile MLD patients (40%), while p.P426L was most frequent in adults (42.5%), which is consistent with earlier observations, although p.P426L was also found in a few late-infantile patients (0.9%), and c.459+1G>A was present in some adults (9%). Mutation c.459+1G>A is more frequent in countries situated at the western edges of Europe, i.e., in Great Britain and Portugal, and also in Belgium, Switzerland, and Italy, which is visible as a strand ranging from North to South, and additionally in Czech and Slovak Republics. Mutation p.P426L is most prevalent in countries assembled in a cluster containing the Netherlands, Germany, and Austria. In other Central European countries, the frequency of both c.459+1G>A and p.P426L ranges from 8 to 37.5%. Our study has confirmed that c.459+1G>A and p.P426L are the most frequently found MLD-causing mutations in Europe. The data about their prevalence reflect the population variability in Europe.

• Authors: Agnieszka Lugowska, Olga Amaral, Johannes Berger, Linda Berna, Nils U Bosshard, Amparo Chabas, Anthony Fensom, Volkmar Gieselmann, Natalia G Gorovenko, Willy Lissens, Jan-Eric Mansson, Ana Marcao, Helen Michelakakis, Hanno Bernheimer, Natalia V Ol'khovych, Stefano Regis, Richard Sinke, Anna Tylki-Szymanska, Barbara Czartoryska
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 86 Issue 3 Pg. 353-9 (Nov 2005) ISSN: 1096-7192 [Print] United States
• PMID: 16140556 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Cerebroside-Sulfatase

Topics

• Adolescent
• Adult
• Cerebroside-Sulfatase (genetics)
• Child
• Child, Preschool
• Europe
• Humans
• Infant
• Leukodystrophy, Metachromatic (enzymology, genetics)
• Mutation