Neurosciences Unit, Health Department of Western Australia, Cnr Mooro Drive and John XXIII Avenue, Mt. Claremont 6019, Western Australia, Australia.
J Neurol Sci. 2011 Feb 15;301(1-2):14-20. doi: 10.1016/j.jns.2010.11.015. Epub 2010 Dec 13.
This study aims to understand the neurological manifestations of patients with an indeterminate CAG repeat length (36-39) of the Huntingtin gene, HTT.
A longitudinal evaluation of 10 patients was performed. Duration of follow-up was mean=4.23 years (standard deviation 1.068; 95% CI 3.466-4.994; range 3-6.4 years). Three patients had a CAG repeat length of 37, three 38 and four 39. Mean CAG repeat length=38 (standard deviation 0.88; 95% CI 37.47-38.73; range 37-39). Data from clinical histories, neurological examinations, the United Huntington's Disease Rating Scale (UHDRS) and MRI imaging were collected.
Four patients developed facial chorea, ataxia, impaired tongue protrusion, abnormal saccades and intermittent eye pursuits, dysarthria and impaired Luria 3 hand test. Early in its natural history the neurological syndrome is dominated by perioral chorea, subtle cognitive deficits and mild ataxia. Three patients developed a formal diagnosis of HD within 5 years. The illness progression was variable and associated with different co-morbidities. MRI scans showed ventricular dilatation as a common finding. Scores from UHDRS, Total Functional Capacity (TFC) and mini-mental state examination (MMSE) suggested significant behavioural and functional impairment with compromised cognitive abilities. Two patients had subtle manifestations and four remained asymptomatic (3 patients CAG=37; 1 patient CAG=39).
This study documents the disease manifestations and natural history of people with CAG repeat lengths within the indeterminate range. The findings reveal heterogeneity in disease progression and have implications on the advice that should be given to patients and families on risk assessment and prognosis. Long-term follow up of such patients is essential as the neurological presentation of indeterminate CAG repeat length mutation might be accelerated by associated medical disorders and treatments, environmental and modifying genetic factors.
本研究旨在了解亨廷顿病基因 HTT 的不确定 CAG 重复长度（36-39）患者的神经表现。
对 10 例患者进行了纵向评估。随访时间平均为 4.23 年（标准差 1.068；95%置信区间 3.466-4.994；范围 3-6.4 年）。3 例患者的 CAG 重复长度为 37，3 例为 38，4 例为 39。平均 CAG 重复长度为 38（标准差 0.88；95%置信区间 37.47-38.73；范围 37-39）。收集了临床病史、神经系统检查、亨廷顿病统一评定量表（UHDRS）和 MRI 影像学数据。
4 例患者出现面口舞蹈症、共济失调、舌突出障碍、异常扫视和间歇性眼球追踪、构音障碍和 Luria 3 手试验障碍。在其自然病史早期，神经系统综合征主要表现为口周舞蹈症、轻微认知障碍和轻度共济失调。3 例患者在 5 年内确诊为 HD。疾病进展存在差异，与不同的合并症相关。MRI 扫描显示脑室扩张是常见的发现。UHDRS、总功能能力（TFC）和简易精神状态检查（MMSE）评分表明存在明显的行为和功能障碍，认知能力受损。2 例患者表现轻微，4 例患者无症状（3 例 CAG=37；1 例 CAG=39）。
本研究记录了处于不确定范围的 CAG 重复长度患者的疾病表现和自然病史。研究结果显示疾病进展存在异质性，这对向患者和家属提供风险评估和预后建议具有重要意义。对这类患者进行长期随访至关重要，因为不确定 CAG 重复长度突变的神经表现可能会因相关的医疗疾病和治疗、环境和修饰基因因素而加速。
