CNP deficiency causes severe hypomyelinating leukodystrophy in humans

AbstractMyelin pathologies are an important cause of multifactorial, e.g., multiple sclerosis, and Mendelian, e.g., leukodystrophy, neurological disorders.CNP encodes a major component of myelin and its CNS expression is exclusive to myelin-forming oligodendrocytes. Deficiency of CNP in mouse causes a lethal white matter neurodegenerative phenotype. However, a corresponding human phenotype has not been described to date. Here, we describe a multiplex consanguineous family from Oman in which multiple affected members display a remarkably consistent phenotype of neuroregression with profound brain white matter loss. A novel homozygous missense variant inCNP was identified by combined autozygome/exome analysis. Immunoblot analysis suggests that this is a null allele in patient fibroblasts, which display abnormal F-actin organization. Our results suggest the establishment of a novelCNP-related hypomyelinating leukodystrophy in humans.
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research