Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive 
neurological disorder characterised by pyramidal, cerebellar, and autonomic 
disturbances. Duplication of the LMNB1 gene is the genetic cause of ADLD, yet 
the pathogenetic mechanism is not defined. In this study, we analysed cells and 
muscle tissue from three patients affected by ADLD, carrying an extra copy of 
the LMNB1 gene. Lamin B1 levels were dramatically increased in ADLD nuclei, both 
in skin fibroblasts and skeletal muscle fibres. Since lamin B1 is known to bind 
Oct-1, a transcription factor involved in the oxidative stress pathway, we 
investigated Oct-1 fate in ADLD. Oct-1 recruitment to the nuclear periphery was 
increased in ADLD cells, while nucleoplasmic localisation of the transcription 
factor under oxidative stress conditions was reduced. Importantly, lamin B1 
degradation occurring in some, but not all ADLD cell lines, slowed down lamin B1 
and Oct-1 accumulation. In skeletal muscle, focal disorganisation of sarcomeres 
was observed, while IIB-myosin heavy chain, an Oct-1 target gene, was 
under-expressed and rod-containing fibres were formed. These data show that a 
high degree of regulation of lamin B1 expression is implicated in the different 
clinical phenotypes observed in ADLD and show that altered Oct-1 nuclear 
localisation contributes to the disease phenotype.