Mutations c.459+1G>A and p.P426L in the ARSA gene: prevalence in metachromatic leukodystrophy patients from European countries.
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.
Lugowska
Agnieszka
A
Institute of Psychiatry and Neurology, Department of Genetics, Warsaw, Poland. alugipin@yahoo.com
Amaral
Olga
O
Berger
Johannes
J
Berna
Linda
L
Bosshard
Nils U
NU
Chabas
Amparo
A
Fensom
Anthony
A
Gieselmann
Volkmar
V
Gorovenko
Natalia G
NG
Lissens
Willy
W
Mansson
Jan-Eric
JE
Marcao
Ana
A
Michelakakis
Helen
H
Bernheimer
Hanno
H
Ol'khovych
Natalia V
NV
Regis
Stefano
S
Sinke
Richard
R
Tylki-Szymanska
Anna
A
Czartoryska
Barbara
B
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
D002553:Cerebroside-Sulfatase