A Novel Duplication Confirms the Involvement of 5q23.2 in Autosomal Dominant Leukodystrophy

• DOI: 10.1001/archneur.65.11.1496
• Publication Date: 2008-11-10T21:19:16Z
• Authors: Inge A. Meijer; Ana A. Simoes-Lopes; Sandra Laurent; Tanya Katz; Judith St-Onge; Dominique J. Verlaan; Nicolas Dupré; Manon Thibault; Johanne Mathurin; Jean-Pierre Bouchard; Guy A. Rouleau
• Keywords: Comparative genomic hybridization; Genetic linkage; Candidate gene

Objective:: To identify the underlying locus and diseasecausing mutation for adult-onset autosomal dominant leukodystrophy (ADLD).Design: Previously, an ADLD on chromosome 5q23 was mapped between markers D5S1495 CTT/CCT15.This region contains 13 known putative candidate genes.A 2-point linkage analysis confirmed of a large multigenerational French Canadian family to 5q23.In addition, screening genes within interval as well 5 neighboring completed, followed by comparative genomic hybridization.Subjects: A with mimicking progressive multiple sclerosis identified studied.Eight affected members were available study presented autonomic dysfunction upper motorneuron signs affecting gait. Results:The thorough gene approach did not any mutation.Consequently, whole-chromosome hybridization 280-kilobase duplication chromosomal band 5q23.2 in 2 individuals.This 3 genes: LMNB1, FLJ36242, MARCH3. Conclusion:We have novel that supports implication duplicated LMNB1 disease-causing mutation.However, additional functional studies lamin B1 overexpression are necessary elucidate involvement myelination degenerative disorders such sclerosis.