Compensating for central nervous system dysmyelination: Females with a proteolipid protein gene duplication and sustained clinical improvement

摘要: A submicroscopic duplication that contains the entire proteolipid protein gene is major cause of Pelizaeus-Merzbacher disease, an X-linked central nervous system dysmyelinating disorder. Previous studies have demonstrated carrier females for are usually asymptomatic. We describe 2 unrelated female patients who present with mild disease or spastic paraplegia. In 1 patient, clinical features as well cranial magnetic resonance imaging and brainstem auditory evoked potential results improved dramatically over a 10-year period. The other presented diplegia was initially diagnosed cerebral palsy, has also shown improvement. Interphase fluorescent in situ hybridization identified both patients. analyses family members indicated occurred de novo events. Neither skewing X inactivation peripheral lymphocytes nor coding alterations were either patient. These findings indicate that, occasionally, can manifest early-onset neurological phenotype. hypothesize remarkable improvement result myelin compensation by oligodendrocytes expressing one copy secondary to selection favorable pattern. plasticity formation suggest role stem cell transplantation therapies.