Cohen S, Masyn K, Adams J, Hessl D, Rivera S, Tassone F, Brunberg J, DeCarli C, Zhang L, Cogswell J, Loesch D, Leehey M, Grigsby J, Hagerman P J, Hagerman R
Department of Human Development, University of California-Davis Medical Center, 2825 50 St., Sacramento, CA 95817, USA.
Neurology. 2006 Oct 24;67(8):1426-31. doi: 10.1212/01.wnl.0000239837.57475.3a.
To assess changes in regional brain volumes associated with the fragile X-associated tremor/ataxia syndrome (FXTAS) and the molecular correlates of these changes.
We administered molecular, MRI, and neurocognitive tests to 36 male premutation carriers (ages 51 to 79), 25 affected and 11 unaffected with FXTAS, and to 21 control subjects of similar age and education.
We found differences among the three groups in whole brain, cerebrum, cerebellum, ventricular volume, and whole-brain white matter hyperintensity, with the affected group showing significantly more pathology than the control and unaffected groups. Brainstem volume was significantly smaller in the unaffected group vs controls but did not differ from the affected group. Within the premutation sample, CGG repeat length correlated with reductions in IQ and cerebellar volume and increased ventricular volume and whole-brain white matter hyperintensity.
The current findings, coupled with recent evidence linking the degree of neuropathology (numbers of intranuclear inclusions) to the size of the premutation allele, provide evidence that the neurodegenerative phenotype in the fragile X-associated tremor/ataxia syndrome is a consequence of the CGG repeat expansion.
评估与脆性X相关震颤/共济失调综合征（FXTAS）相关的脑区体积变化及其分子关联。
我们对36名男性前突变携带者（年龄51至79岁）进行了分子、MRI和神经认知测试，其中25名患有FXTAS，11名未患FXTAS，并对21名年龄和教育程度相似的对照受试者进行了测试。
我们发现三组在全脑、大脑、小脑、脑室体积和全脑白质高信号方面存在差异，患病组的病理表现明显多于对照组和未患病组。未患病组的脑干体积明显小于对照组，但与患病组无差异。在前突变样本中，CGG重复长度与智商降低、小脑体积减小以及脑室体积增加和全脑白质高信号增加相关。
目前的研究结果，加上最近将神经病理学程度（核内包涵体数量）与前突变等位基因大小联系起来的证据，表明脆性X相关震颤/共济失调综合征中的神经退行性表型是CGG重复扩增的结果。
