Heterogeneous patterns of tissue injury in NARP syndrome

摘要: Point mutations at m.8993T>C and m.8993T>G of the mtDNA ATPase 6 gene cause neurogenic weakness, ataxia retinitis pigmentosa (NARP) syndrome, a mitochondrial disorder characterized by retinal, central peripheral neurodegeneration. We performed detailed neurological, neuropsychological ophthalmological phenotyping mother four daughters with NARP syndrome from mutation, including 3-T brain MRI, spectral domain optical coherence tomography (SD-OCT), adaptive optics scanning laser ophthalmoscopy (AOSLO), electromyography nerve conduction studies (EMG-NCS) formal testing. The degree mutant heteroplasmy for mutation was evaluated real-time allele refractory system quantitative PCR hair bulbs (ectoderm) blood leukocytes (mesoderm). There were marked phenotypic differences between family members, even individuals greatest degrees ectodermal mesodermal heteroplasmy. MRI revealed cerebellar atrophy cystic cavitary T2 hyperintensities in basal ganglia. SD-OCT demonstrated similarly heterogeneous areas neuronal axonal loss inner outer retinal layers. AOSLO showed increased cone spacing due to photoreceptor loss. EMG-NCS varying length-dependent sensorimotor polyneuropathy. On testing, there deficits processing speed, visual–spatial functioning verbal fluency high rates severe depression. Many these cognitive likely localize and/or ganglia dysfunction. High-resolution imaging analogous patterns tissue injury