Persichetti F, Srinidhi J, Kanaley L, Ge P, Myers R H, D'Arrigo K, Barnes G T, MacDonald M E, Vonsattel J P, Gusella J F
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Neurobiol Dis. 1994 Dec;1(3):159-66. doi: 10.1006/nbdi.1994.0019.
CAG repeat expansion in the Huntington's disease gene (HD) was examined in postmortem brains from 310 clinically diagnosed and 15 'at risk' individuals. Presence of an expanded CAG allele (>37 units) was the cause of the disorder in almost all cases (307 of 310). Despite a diversity of reporting clinicians, neurological and psychiatric onset and age at death all displayed significant inverse correlations with CAG number indicating that diagnosis of onset is reasonably accurate, and that most patients die from the disease and its complications. Neuronal changes before clinical onset are not detected by conventional microscopic examination as three out of 15 'at risk' brains had an expanded CAG allele but no neuropathology. The cause of HD-like neuropathology in three exceptional brains from clinically diagnosed individuals is unclear. The disorder in these cases could be an HD phenocopy or result from alternative mutational mechanisms at the HD locus.
在310例临床诊断患者和15例“有患病风险”个体的尸检大脑中，对亨廷顿舞蹈症基因（HD）中的CAG重复序列扩增情况进行了检测。几乎在所有病例中（310例中的307例），CAG等位基因的扩增（>37个单位）都是导致该疾病的原因。尽管报告的临床医生各不相同，但神经和精神症状的发作以及死亡年龄均与CAG数目呈显著负相关，这表明发病诊断相当准确，且大多数患者死于该疾病及其并发症。常规显微镜检查未检测到临床发作前的神经元变化，因为15例“有患病风险”的大脑中有3例存在CAG等位基因扩增，但无神经病理学改变。临床诊断个体的3例特殊大脑中出现类似HD的神经病理学改变的原因尚不清楚。这些病例中的疾病可能是HD的表型模拟，或者是由HD基因座的其他突变机制导致的。
