Heterogeneous patterns of tissue injury in NARP syndrome.
Heterogeneous patterns of tissue injury in NARP syndrome.
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DOI：
10.1007/s00415-010-5775-1
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发表时间：
2011-03
影响因子：
6
通讯作者：
Green AJ
中科院分区：
文献类型：
--
作者：
Gelfand JM;Duncan JL;Racine CA;Gillum LA;Chin CT;Zhang Y;Zhang Q;Wong LJ;Roorda A;Green AJ
mtDNA ATP酶6基因m.8993T>C和m.8993T>G点突变导致神经源性虚弱、共济失调和视网膜色素变性（NARP）综合征，这是一种以视网膜、中枢和外周神经变性为特征的线粒体疾病。我们对一位母亲和四个女儿进行了详细的神经学、神经心理学和眼科表型分析，包括3-T脑MRI、光谱域光学相干断层扫描（SD-OCT）、自适应光学扫描激光检眼镜（AOSLO）、肌电图和神经传导研究（EMG-NCS）和正式的神经心理学测试。通过实时等位基因难治突变系统定量PCR检测来自毛球（外胚层）和血白细胞（中胚层）的mtDNA，评估m.8993T>C突变的突变异质性程度。家庭成员之间有显着的表型差异，即使是最大程度的外胚层和中胚层异质性的个人之间。3-T MRI显示小脑萎缩和基底节囊状和空洞状T2高信号。SD-OCT显示了视网膜内层和外层中类似的神经元和轴突损失的异质区域。AOSLO显示由于光感受器损失而增加的视锥间距。EMG NCS显示不同程度的长度依赖性感觉运动轴突性多发性神经病。在正式的神经心理学测试中，有不同程度的处理速度，视觉空间功能和语言流畅性方面的缺陷，以及严重抑郁症的高比率。这些认知缺陷中的许多可能局限于小脑和/或基底神经节功能障碍。NARP综合征的高分辨率视网膜和脑成像显示了类似的组织损伤模式，其特征是神经元丢失的异质性区域。本文的在线版本（doi：10.1007/s 00415 -010-5775-1）包含补充材料，可供授权用户使用。
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 online version of this article (doi:10.1007/s00415-010-5775-1) contains supplementary material, which is available to authorized users.
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影响因子：
13.7
作者：
Hayashi, N;Geraghty, MT;Green, WR
通讯作者：
Green, WR
影响因子：
2
作者：
Morava, E;Rodenburg, RJ;Smeitink, J
通讯作者：
Smeitink, J
影响因子：
8.6
作者：
Aarsland, Dag;Marsh, Laura;Schrag, Anette
通讯作者：
Schrag, Anette
DOI：
10.1038/nrg1606
发表时间：
2005-05
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Duncan, Jacque L.;Zhang, Yuhua;Roorda, Austin
通讯作者：
Roorda, Austin