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A single mutation in the GALC gene is responsible for the majority of late onset Krabbe disease patients in the Catania (Sicily, Italy) region
Author(s) -
Lissens Willy,
Arena Alessia,
Seneca Sara,
Rafi Mohammad,
Sorge Giovanni,
Liebaers Inge,
Wenger David,
Fiumara Agata
Publication year - 2007
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9500
Subject(s) - frameshift mutation , missense mutation , biology , mutation , genetics , haplotype , founder effect , allele , krabbe disease , gene , disease , leukodystrophy , medicine
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. © 2007 Wiley‐Liss, Inc.