FIGURE 1.

Genomic rearrangements involving the LMNB1 gene cause the demyelinating disorder Autosomal Dominant Leukodystrophy (ADLD). (A) ADLD patient MRI (Fluid-attenuated inversion recovery sequence) reveals white matter hyperintensities indicating myelin pathology (marked by arrows). (B) ADLD patient brain showing patchy areas of myelin loss marked by asterisk (^∗). Plus sign (+) indicates normal myelin. (C) Histopathological analysis of ADLD brain section using Luxol Fast Blue, a myelin stain, exhibits areas of pale staining and vacuolar demyelination, marked by asterisks (^∗). Plus sign (+) indicates normal myelin staining. (D) Genomic region on chromosome 5q23.2 that contains the LMNB1 gene. Blue bars indicate genomic duplications from two individual patients that have centromeric and telomeric junctions closest to the LMNB1 gene that allow the identification of the minimal critical region required for disease causation (dashed line). Red bar indicates the deletion upstream of the LMNB1 gene responsible for a variant ADLD phenotype reported in a single family. Data for (D) is modified from Giorgio et al. (2015). Black bars indicate the location of genes encompassed by the genomic rearrangements and the direction of transcription.