OBJECTIVE: To characterize the genetic and clinical features of patients with 
autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) carrying 
duplication and deletion upstream of lamin B1 (LMNB1).
METHODS: Ninety-three patients with adult-onset leukoencephalopathy of unknown 
etiology were genetically analyzed for copy numbers of LMNB1 and its upstream 
genes. We examined LMNB1 expression by reverse transcription-qPCR using total 
RNA extracted from peripheral leukocytes. Clinical and MRI features of the 
patients with ADLD were retrospectively analyzed.
RESULTS: We identified 4 patients from 3 families with LMNB1 duplication. The 
duplicated genomic regions were different from those previously reported. The 
mRNA expression level of LMNB1 in patients with duplication was significantly 
increased. The clinical features of our patients with LMNB1 duplication were 
similar to those reported previously, except for the high frequency of cognitive 
impairment in our patients. We found 2 patients from 1 family carrying a 249-kb 
genomic deletion upstream of LMNB1. Patients with the deletion exhibited 
relatively earlier onset, more prominent cognitive impairment, and fewer 
autonomic symptoms than patients with duplication. The presence of cerebellar 
symptoms and lesions may be characteristic in our patients with the deletion 
compared with the previously reported family with the deletion. Magnetic 
resonance images of patients with the deletion exhibited a widespread 
distribution of white matter lesions including the anterior temporal region.
CONCLUSIONS: We identified 4 Japanese families with ADLD carrying duplication or 
deletion upstream of LMNB1. There are differences in clinical and MRI features 
between the patients with the duplication and those with the deletion upstream 
of LMNB1.