Different patterns of electrophysiological deficits in manifesting and non-manifesting carriers of the DYT1 gene mutation
Different patterns of electrophysiological deficits in manifesting and non-manifesting carriers of the DYT1 gene mutation
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DOI：
10.1093/brain/awg209
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发表时间：
2003-09-01
期刊：
影响因子：
14.5
通讯作者：
Bhatia, KP
中科院分区：
文献类型：
--
作者：
Edwards, MJ;Huang, YZ;Bhatia, KP
染色体9q34上DYT1基因的突变导致早发性原发性扭转肌张力障碍，具有常染色体显性遗传，但表型外显率低。本研究的目的是通过比较临床上受DYT1基因突变影响和未受DYT1基因突变影响的携带者的皮层和脊髓回路的电生理，来评估DYT1基因的功能后果。我们评估了10例DYT1显性基因携带者（MDYT1）、7例DYT1非显性基因携带者（NMDYT1）和13例健康对照者的皮质内抑制（ICI）、皮质内促进（ICF）、皮质沉默期（SP）和脊髓互抑（RI）。MDYT1受试者的异常与先前对原发性肌张力障碍的非遗传特征个体的研究相似。与健康对照组相比，他们的ICI减少，SP缩短，RI突触前期缺失。NMDYT1受试者的皮质抑制（ICI和SP）也显著降低，但他们的脊髓RI与对照组没有差异。我们得出结论，肌张力障碍的临床表现取决于广泛的电生理缺陷，而DYT1基因突变本身的存在只会导致这些变化的一个子集。这与可能需要额外的环境/遗传损伤来揭示DYT1基因携带者的临床症状的假设是一致的。
A mutation in the DYT1 gene on chromosome 9q34 causes early-onset primary torsion dystonia with autosomal dominant inheritance but low phenotypic penetrance. The aim of the present study was to assess the functional consequences of the DYT1 gene, by comparing the electrophysiology of cortical and spinal circuits in clinically affected and unaffected carriers of the DYT1 gene mutation. We assessed intracortical inhibition (ICI), intracortical facilitation (ICF), the cortical silent period (SP) and spinal reciprocal inhibition (RI) in 10 manifesting DYT1 gene carriers (MDYT1), seven non-manifesting DYT1 gene carriers (NMDYT1) and 13 healthy controls. The MDYT1 subjects had abnormalities similar to those seen in previous studies of non-genetically characterized individuals with primary dystonia. They had reduced ICI, shorter SP and absent presynaptic phase of RI compared with the healthy controls. NMDYT1 subjects also had a significant reduction in cortical inhibition (ICI and SP), but their spinal RI was not different from controls. We conclude that clinical expression of dystonia depends on widespread electrophysiological deficits, and the presence of the DYT1 gene mutation itself leads only to a subset of these changes. This is consistent with the hypothesis that additional environmental/genetic insults may be needed to reveal clinical symptoms in DYT1 gene carriers.