caa a22 4500 445808861 CHVBK 20180317145205.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00415-010-5775-1 doi (NATIONALLICENCE)springer-10.1007/s00415-010-5775-1 Heterogeneous patterns of tissue injury in NARP syndrome [Elektronische Daten] [Jeffrey Gelfand, Jacque Duncan, Caroline Racine, Leslie Gillum, Cynthia Chin, Yuhua Zhang, Qing Zhang, Lee-Jun Wong, Austin Roorda, Ari Green] Point mutations at m.8993T>C and m.8993T>G of the mtDNA ATPase 6 gene cause the neurogenic weakness, ataxia and retinitis pigmentosa (NARP) syndrome, a mitochondrial disorder characterized by retinal, central and peripheral neurodegeneration. We performed detailed neurological, neuropsychological and ophthalmological phenotyping of a mother and four daughters with NARP syndrome from the mtDNA m.8993T>C ATPase 6 mutation, including 3-T brain MRI, spectral domain optical coherence tomography (SD-OCT), adaptive optics scanning laser ophthalmoscopy (AOSLO), electromyography and nerve conduction studies (EMG-NCS) and formal neuropsychological testing. The degree of mutant heteroplasmy for the m.8993T>C mutation was evaluated by real-time allele refractory mutation system quantitative PCR of mtDNA from hair bulbs (ectoderm) and blood leukocytes (mesoderm). There were marked phenotypic differences between family members, even between individuals with the greatest degrees of ectodermal and mesodermal heteroplasmy. 3-T MRI revealed cerebellar atrophy and cystic and cavitary T2 hyperintensities in the basal ganglia. SD-OCT demonstrated similarly heterogeneous areas of neuronal and axonal loss in inner and outer retinal layers. AOSLO showed increased cone spacing due to photoreceptor loss. EMG-NCS revealed varying degrees of length-dependent sensorimotor axonal polyneuropathy. On formal neuropsychological testing, there were varying deficits in processing speed, visual-spatial functioning and verbal fluency and high rates of severe depression. Many of these cognitive deficits likely localize to cerebellar and/or basal ganglia dysfunction. High-resolution retinal and brain imaging in NARP syndrome revealed analogous patterns of tissue injury characterized by heterogeneous areas of neuronal loss. The Author(s), 2010 Mitochondrial disorders nationallicence Neuroophthalmology nationallicence Neuropsychology nationallicence Cerebellar disease nationallicence Neuropathy nationallicence Gelfand Jeffrey Department of Neurology, University of California, 94143-0114, San Francisco, CA, USA aut Duncan Jacque Department of Ophthalmology, University of California, San Francisco, CA, USA aut Racine Caroline Department of Neurology, University of California, 94143-0114, San Francisco, CA, USA aut Gillum Leslie Department of Neurology, University of California, 94143-0114, San Francisco, CA, USA aut Chin Cynthia Department of Radiology, University of California, San Francisco, CA, USA aut Zhang Yuhua School of Optometry, University of California, Berkeley, CA, USA aut Zhang Qing Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, IN, USA aut Wong Lee-Jun Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA aut Roorda Austin School of Optometry, University of California, Berkeley, CA, USA aut Green Ari Department of Neurology, University of California, 94143-0114, San Francisco, CA, USA aut Journal of Neurology Springer-Verlag 258/3(2011-03-01), 440-448 0340-5354 258:3<440 2011 258 415 https://doi.org/10.1007/s00415-010-5775-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00415-010-5775-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gelfand Jeffrey Department of Neurology, University of California, 94143-0114, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Duncan Jacque Department of Ophthalmology, University of California, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Racine Caroline Department of Neurology, University of California, 94143-0114, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Gillum Leslie Department of Neurology, University of California, 94143-0114, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Chin Cynthia Department of Radiology, University of California, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Zhang Yuhua School of Optometry, University of California, Berkeley, CA, USA aut NATIONALLICENCE 700 1- Zhang Qing Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, IN, USA aut NATIONALLICENCE 700 1- Wong Lee-Jun Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA aut NATIONALLICENCE 700 1- Roorda Austin School of Optometry, University of California, Berkeley, CA, USA aut NATIONALLICENCE 700 1- Green Ari Department of Neurology, University of California, 94143-0114, San Francisco, CA, USA aut NATIONALLICENCE 773 0- Journal of Neurology Springer-Verlag 258/3(2011-03-01), 440-448 0340-5354 258:3<440 2011 258 415 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer