Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating 
disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, 
as only a few cases have been analyzed in detail, the mechanisms underlying 
LMNB1 duplications are unclear. We report the detailed molecular analysis of the 
largest collection of ADLD families studied, to date. We have identified the 
minimal duplicated region necessary for the disease, defined all the duplication 
junctions at the nucleotide level and identified the first inverted LMNB1 
duplication. We have demonstrated that the duplications are not recurrent; 
patients with identical duplications share the same haplotype, likely inherited 
from a common founder and that the duplications originated from intrachromosomal 
events. The duplication junction sequences indicated that nonhomologous end 
joining or replication-based mechanisms such fork stalling and template 
switching or microhomology-mediated break induced repair are likely to be 
involved. LMNB1 expression was increased in patients' fibroblasts both at mRNA 
and protein levels and the three LMNB1 alleles in ADLD patients show equal 
expression, suggesting that regulatory regions are maintained within the 
rearranged segment. These results have allowed us to elucidate duplication 
mechanisms and provide insights into allele-specific LMNB1 expression levels.