Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers
Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers
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DOI：
10.1093/brain/awf184
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发表时间：
2002-08-01
期刊：
影响因子：
14.5
通讯作者：
Hagerman, P. J.
中科院分区：
文献类型：
--
作者：
Greco, C. M.;Hagerman, R. J.;Hagerman, P. J.
最近在一些携带脆性X综合征（FXS）脆性X智力发育迟滞基因（FMR1）突变前等位基因的成年男性中发现了一种神经系统综合征，包括进行性行动性震颤伴共济失调、认知能力下降和广泛性脑萎缩。神经组织学研究现在已经在四个老年突变前携带者的大脑上进行，以前没有报道，他们表现出神经表型。嗜酸性核内包涵体存在于所有4个个体的皮层神经元核和星形细胞核中。对其中两名携带者的大脑进行系统分析表明，核内包涵体遍布大脑和脑干，在海马体中数量最多。小脑浦肯野细胞、浦肯野轴突鱼雷和伯格曼胶质瘤明显消失。浦肯野细胞核内包涵体不存在，但在齿状核的少量神经元和小脑星形胶质细胞中弥漫性存在。所有四名FXS携带者的大脑中都存在内含物，这些神经学发现进一步支持了与突变前FMR1等位基因相关的独特临床实体。虽然这些突变前携带者的FMR1 mRNA水平升高可能导致神经病理改变，但包裹体的起源尚不清楚。
A neurological syndrome involving progressive action tremor with ataxia, cognitive decline and generalized brain atrophy has been described recently in some adult males with pre-mutation alleles of the fragile X syndrome (FXS) fragile X mental retardation gene (FMR1). Neurohistological studies have now been performed on the brains of four elderly premutation carriers, not reported previously, who displayed the neurological phenotype. Eosinophilic, intranuclear inclusions were present in both neuronal and astrocytic nuclei of the cortex in all four individuals. Systematic analysis of the brains of two of these carriers demonstrated the presence of the intranuclear inclusions throughout the cerebrum and brainstem, being most numerous in the hippocampal formation. The cerebellum displayed marked dropout of Purkinje cells, Purkinje axonal torpedoes and Bergmann gliosis. Intranuclear inclusions were absent from Purkinje cells, although they were present in a small number of neurones in the dentate nucleus and diffusely in cerebellar astrocytes. The presence of inclusions in the brains of all four FXS carriers with the neurological findings provides further support for a unique clinical entity associated with pre-mutation FMR1 alleles. The origin of the inclusions is unknown, although elevated FMR1 mRNA levels in these pre-mutation carriers may lead to the neuropathological changes.