Gene-Related Cerebellar Neurodegeneration in SCA3/MJD: A Case-Controlled Imaging-Genetic Study
Gene-Related Cerebellar Neurodegeneration in SCA3/MJD: A Case-Controlled Imaging-Genetic Study
复制标题
SCA3/MJD 中基因相关的小脑神经变性：病例对照影像遗传学研究
DOI：
10.3389/fneur.2019.01025
复制
发表时间：
2019-09-24
影响因子：
3.4
通讯作者：
Jiang, Hong
中科院分区：
文献类型：
--
作者：
Peng, Huirong;Liang, Xiaochun;Jiang, Hong
背景：脊髓小脑型共济失调3型/马查多-约瑟夫病(SCA3/MJD)是由ATXN3基因编码序列内CAG重复扩增引起的9种多谷氨酰胺(PolyQ)病之一。很少有人对宏观和微观结构变化进行多模式成像分析。方法：采用结构磁共振成像(SMRI)、质子磁共振波谱(1H-MRS)和扩散张量成像(DTI)对31例经遗传确诊的SCA3/MJD患者和31例健康人进行多模式神经成像研究。结果：SCA3/MJD患者小脑、脑桥、中脑、延髓、额下回、脑岛、左侧额上回灰质体积明显缩小。国际协作性共济失调评定量表(ICars)总分与小脑、桥脑和中脑灰质体积呈负相关。扩展等位基因的CAG重复数与小脑皮质呈负相关。SCA3/MJD患者小脑中脚、齿状核、小脑鞭、丘脑的NAA/Cr和NAA/Cho比值较正常对照组明显降低，提示SCA3/MJD患者小脑发生了神经化学改变。基于脑束的空间统计学(TBSS)分析显示小脑脚的体积和平均FA值显著降低，这与我们的患者的ICAR总分呈负相关。结论：在本研究中，基于组织体积、神经化学和组织微结构，我们证实了SCA3/MJD的小脑变性。此外，临床指标、小脑变性和遗传变异之间的关联支持SCA3/MJD中不同的基因-表型关系。
Background: Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is one of the nine polyglutamine (polyQ) diseases and is caused by a CAG repeat expansion within the coding sequence of the ATXN3 gene. Few multimodal imaging analyses of the macro- and micro-structural changes have been performed. Methods: In the present study, we recruited 31 genetically-confirmed symptomatic SCA3/MJD patients and 31 healthy subjects as controls for a multimodal neuroimaging study using structural magnetic resonance imaging (sMRI), proton magnetic resonance spectroscopy (1H-MRS) and diffusion tensor imaging (DTI). Results: The SCA3/MJD patients displayed a significantly reduced of gray matter volume in the cerebellum, pons, midbrain and medulla, as well as inferior frontal gyrus and insula, and left superior frontal gyrus. The total International Cooperative Ataxia Rating Scale (ICARS) score was inversely correlated with the gray matter volume in the cerebellar culmen, pons and midbrain. The numbers of CAG repeats in the expanded alleles were inversely correlated with the gray matter in the cerebellar culmen. NAA/Cr and NAA/Cho ratio in the middle cerebellar peduncles, dentate nucleus, cerebellar vermis, and thalamus in the SCA3/MJD patients were significantly reduced when compared to that in the normal controls, suggesting neurochemical alterations in cerebellum in the SCA3/MJD patients. Tract-Based Spatial Statistics (TBSS) analysis revealed significant lower volume and mean FA values of the cerebellar peduncles, which inversely correlated with the total scores of ICARS in our patients. Conclusions: In this study, we demonstrated cerebellar degeneration in SCA3/MJD based on tissue volume, neurochemistry, and tissue microstructure. Moreover, the associations between the clinical measures, cerebellar degeneration and genetic variation support a distinct genotype-phenotype relationship in SCA3/MJD.