Xuereb J H, MacMillan J C, Snell R, Davies P, Harper P S
Department of Pathology, University of Cambridge, UK.
J Neurol Neurosurg Psychiatry. 1996 Jan;60(1):78-81. doi: 10.1136/jnnp.60.1.78.
To correlate the degree of CAG repeat expansion with neuropathological findings in Huntington's disease.
The CAG repeat polymorphism was analysed in a large series of brain samples from 268 patients with a clinical diagnosis of Huntington's disease in which full neuropathological data was available.
Analysis by polymerase chain reaction was successful in 63% of samples (169 of 268). Repeat expansions were detected in 152 of 153 (99%) samples with a neuropathological diagnosis of Huntington's disease. The exceptional case (22 CAG repeats) showed mild but definite pathological changes and had a typical clinical illness with a positive family history; it raises the possibility that an alternative mutation in the Huntington's disease gene may be responsible although it is more likely that a mutation in another gene has resulted in an Huntington's disease-like phenotype. Four of 16 cases without pathological changes of Huntington's disease also possessed an expanded repeat sequence; a glioblastoma masked the pathological changes of Huntington's disease in one case but the other three cases had a typical clinical history and a positive family history. These three cases may reliably be classified as Vonsattel's Huntington's disease grade 0. Three of 12 cases with a normal repeat length and no morphological changes of Huntington's disease showed other neuropathology; two had Alzheimer's disease and the other had multiple sclerosis. Review of the clinical notes of two other cases indicated a diagnosis of tardive dyskinesia complicating phenothiazine treatment of schizophrenia. The remaining pathology negative/expansion negative cases had been referred because of a family history of Huntington's disease; all but one were themselves symptom free. Apart from emphasising the possibility that an alternative mutation may result in a clinical phenocopy of Huntington's disease, this case suggests that such a clinical phenocopy may occur without gross or light microscopical neuropathological changes (Vonsattel's Huntington's disease grade 0).
The study confirms the value of molecular genetic analysis in cases of suspected Huntington's disease and shows the importance of detailed neuropathological study in the few cases of suspected Huntington's disease with normal CAG repeat lengths.
将亨廷顿舞蹈病中CAG重复序列扩展的程度与神经病理学发现相关联。
对268例临床诊断为亨廷顿舞蹈病且有完整神经病理学数据的大量脑样本进行CAG重复序列多态性分析。
聚合酶链反应分析在63%的样本（268例中的169例）中成功。在153例经神经病理学诊断为亨廷顿舞蹈病的样本中有152例（99%）检测到重复序列扩展。例外的病例（22个CAG重复序列）显示出轻度但明确的病理变化，有典型的临床病症和阳性家族史；这增加了一种可能性，即亨廷顿舞蹈病基因中的另一种突变可能起作用，尽管更有可能是另一个基因中的突变导致了类似亨廷顿舞蹈病的表型。16例无亨廷顿舞蹈病病理变化的病例中有4例也具有扩展的重复序列；1例胶质母细胞瘤掩盖了亨廷顿舞蹈病的病理变化，但其他3例有典型的临床病史和阳性家族史。这3例可可靠地归类为冯·萨特尔亨廷顿舞蹈病0级。12例重复长度正常且无亨廷顿舞蹈病形态学变化的病例中有3例显示出其他神经病理学改变；2例患有阿尔茨海默病，另1例患有多发性硬化症。对另外2例病例临床记录的回顾表明诊断为迟发性运动障碍，这是吩噻嗪治疗精神分裂症的并发症。其余病理阴性/扩展阴性的病例因亨廷顿舞蹈病家族史而被转诊；除1例之外均无症状。除了强调另一种突变可能导致亨廷顿舞蹈病临床拟表型的可能性外，该病例表明这种临床拟表型可能在无大体或光学显微镜下神经病理学变化（冯·萨特尔亨廷顿舞蹈病0级）的情况下发生。
该研究证实了分子遗传学分析在疑似亨廷顿舞蹈病病例中的价值，并显示了在少数CAG重复长度正常的疑似亨廷顿舞蹈病病例中进行详细神经病理学研究的重要性。
