title: 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.affiliation: Institute of Psychiatry and Neurology, Department of Genetics, Warsaw, Poland. alugipin@yahoo.com
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Lugowska
authors.forename: Olga
authors.initials: O
authors.lastname: Amaral
authors.forename: Johannes
authors.initials: J
authors.lastname: Berger
authors.forename: Linda
authors.initials: L
authors.lastname: Berna
authors.forename: Nils U
authors.initials: NU
authors.lastname: Bosshard
authors.forename: Amparo
authors.initials: A
authors.lastname: Chabas
authors.forename: Anthony
authors.initials: A
authors.lastname: Fensom
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gieselmann
authors.forename: Natalia G
authors.initials: NG
authors.lastname: Gorovenko
authors.forename: Willy
authors.initials: W
authors.lastname: Lissens
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Mansson
authors.forename: Ana
authors.initials: A
authors.lastname: Marcao
authors.forename: Helen
authors.initials: H
authors.lastname: Michelakakis
authors.forename: Hanno
authors.initials: H
authors.lastname: Bernheimer
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Ol'khovych
authors.forename: Stefano
authors.initials: S
authors.lastname: Regis
authors.forename: Richard
authors.initials: R
authors.lastname: Sinke
authors.forename: Anna
authors.initials: A
authors.lastname: Tylki-Szymanska
authors.forename: Barbara
authors.initials: B
authors.lastname: Czartoryska
mesh_terms: D000293:Adolescent; D000328:Adult; D002553:Cerebroside-Sulfatase / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005060:Europe; D006801:Humans; D007223:Infant; D007966:Leukodystrophy, Metachromatic / Q000201:enzymology* / Q000235:genetics; D009154:Mutation
chemical_list: D002553:Cerebroside-Sulfatase