title: A single mutation in the GALC gene is responsible for the majority of late onset Krabbe disease patients in the Catania (Sicily, Italy) region.
abstract: A high proportion of patients with late onset forms of Krabbe disease is observed in a region north of Catania in Sicily. Molecular analysis in five families from this region shows that this condition is mainly due to a not previously described p.Gly41Ser substitution in the GALC gene that abolishes catalytic activity of the galactocerebrosidase enzyme, as shown by expression studies. Three patients were homozygous for this mutation, the other two were heterozygous, one with a frameshift mutation and one with a missense mutation on the second allele. Therefore, the mutation must be a mild one since it leads to late onset disease in all patients. In addition, it is on a unique haplotype indicating that it represents a founder mutation. This is also supported by the fact that the mutation was not found in three late onset patients from other regions in Sicily, in whom four novel mutations were identified.
authors.affiliation: Center for Medical Genetics, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Willy
authors.initials: W
authors.lastname: Lissens
authors.forename: Alessia
authors.initials: A
authors.lastname: Arena
authors.forename: Sara
authors.initials: S
authors.lastname: Seneca
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rafi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sorge
authors.forename: Inge
authors.initials: I
authors.lastname: Liebaers
authors.forename: David
authors.initials: D
authors.lastname: Wenger
authors.forename: Agata
authors.initials: A
authors.lastname: Fiumara
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D018076:DNA, Complementary; D018703:Founder Effect; D016368:Frameshift Mutation; D005698:Galactosylceramidase / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D007558:Italy; D007965:Leukodystrophy, Globoid Cell / Q000235:genetics*; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction
chemical_list: D018076:DNA, Complementary; D005698:Galactosylceramidase