CAG repeat size correlates to electrophysiological motor and sensory phenotypes in SBMA
CAG repeat size correlates to electrophysiological motor and sensory phenotypes in SBMA
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DOI：
10.1093/brain/awm289
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发表时间：
2008-01-01
期刊：
影响因子：
14.5
通讯作者：
Sobue, Gen
中科院分区：
文献类型：
--
作者：
Suzuki, Keisuke;Katsuno, Masahisa;Sobue, Gen
脊髓延髓肌萎缩症（SBMA）是一种由雄激素受体（AR）基因CAG重复序列异常延长引起的成人发作的下运动神经元疾病。主要症状是延髓、面部和四肢肌肉的无力和萎缩，但SBMA患者经常出现感觉障碍。运动症状归因于突变型AR在下运动神经元的核中的积累，这在具有较长CAG重复的患者中更为深刻。我们研究了神经传导特性，包括F波，共106例患者的基因证实SBMA（平均年龄在数据收集53.8岁，范围3175年）和85名对照组。与正常对照组相比，SBMA患者的运动传导速度（MCV）、复合肌肉动作电位（CMAP）、感觉传导速度（SCV）和感觉神经动作电位（SNAP）均显著降低，表明轴突变性是运动和感觉神经的主要过程。上肢的神经比下肢的神经有更严重的异常。正中神经F波缺如30例（28.3%），胫神经无缺如。从CMAP和SNAP之间的关系的分析，患者被确定为具有不同的电生理表型：运动优势，感觉优势和非显性表型。CAG重复序列的大小和发病年龄在运动和感觉显性表型患者之间存在显著差异，表明较长的CAG重复序列与运动显性表型更密切相关，较短的CAG重复序列与感觉显性表型更密切相关。此外，当我们根据CAG重复序列大小对患者进行分类时，CMAP值在CAG重复序列较长的患者中显示出降低的趋势（47），而SNAP在CAG重复序列较短的患者中显著降低（47）。此外，我们发现，在感觉神经元细胞质中的聚集频率往往与CAG重复序列大小呈负相关的尸检研究，支持的观点，即CAG重复序列大小差异与运动和感觉显性表型相关。总之，我们的研究结果表明，有明确的电生理表型的影响CAG重复序列大小在SBMA。
Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, lower motor neuron disease caused by an aberrant elongation of a CAG repeat in the androgen receptor (AR) gene. The main symptoms are weakness and atrophy of bulbar, facial and limb muscles, but sensory disturbances are frequently found in SBMA patients. Motor symptoms have been attributed to the accumulation of mutant AR in the nucleus of lower motor neurons, which is more profound in patients with a longer CAG repeat. We examined nerve conduction properties including F-waves in a total of 106 patients with genetically confirmed SBMA (mean age at data collection 53.8 years; range 3175 years) and 85 control subjects. Motor conduction velocities (MCV), compound muscle action potentials (CMAP), sensory conduction velocities (SCV) and sensory nerve action potentials (SNAP) were significantly decreased in all nerves examined in the SBMA patients compared with that in the normal controls, indicating that axonal degeneration is the primary process in both motor and sensory nerves. More profound abnormalities were observed in the nerves of the upper limbs than in those of the lower limbs. F-waves in the median nerve were absent in 30 of 106 cases (28.3), but no cases of absent F-waves were observed in the tibial nerve. From an analysis of the relationship between CMAPs and SNAPs, patients were identified with different electrophysiological phenotypes: motor-dominant, sensory-dominant and non-dominant phenotypes. The CAG repeat size and the age at onset were significantly different among the patients with motor- and sensory-dominant phenotypes, indicating that a longer CAG repeat is more closely linked to the motor-dominant phenotype and a shorter CAG repeat is more closely linked to the sensory-dominant phenotype. Furthermore, when we classified the patients by CAG repeat size, CMAP values showed a tendency to be decreased in patients with a longer CAG repeat (47), while SNAPs were significantly decreased in patients with a shorter CAG repeat (47). In addition, we found that the frequency of aggregation in the sensory neuron cytoplasm tended to inversely correlate with the CAG repeat size in the autopsy study, supporting the view that the CAG repeat size differentially correlates with motor- and sensory-dominant phenotypes. In conclusion, our results suggest that there are unequivocal electrophysiological phenotypes influenced by CAG repeat size in SBMA.