摘要：

目的 总结青少年型亨廷顿病患者临床表型及IT15 基因胞嘧啶-腺嘌呤-鸟嘌呤（CAG）重复突变特点。 方法 采用聚合酶链反应结合荧光标记毛细管电泳片段分析方法，对159 个亨廷顿病家系272 名成员进行IT15 基因CAG 重复序列检测，并对其中10 例青少年期发病患者的临床表现、影像学特征以及临床表型与基因型相关性进行分析。 结果 经基因检测共发现211 例携带异常扩展的IT15 基因CAG 重复序列，其中10 例为青少年型亨廷顿病患者，临床表现各异，主要以不自主运动和认知功能障碍为主；发病年龄平均（12.50 ± 4.55）岁，IT15 基因CAG 重复序列平均（63.70 ± 14.83）个，Pearson 相关分析显示，二者呈负相关关系（r = - 0.865，P = 0.001）。 结论 青少年型亨廷顿病与成年型亨廷顿病患者临床表现不同，前者主要表现为认知功能障碍；对于无明确家族史、临床表现疑似亨廷顿病的患者，基因检测是明确诊断的依据；亨廷顿病发病年龄与IT15 基因CAG 重复次数呈负相关，但不能完全解释发病年龄的变异性，尤以青少年型亨廷顿病患者显著，可能存在其他遗传调节因素。

关键词: 杭廷顿病, 青少年, 表型, 基因, 突变, 系谱

Abstract:

Objective  To investigate the clinical features and dynamic mutation of 10 cases with juvenile-onset Huntington's disease (HD).  Methods  The cytosine-adenine-guanine (CAG) repeats of IT15 gene were detected by polymerase chain reaction (PCR) and capillary electrophoresis in 272 individuals of 159 pedigrees with preliminary diagnosis of HD. The correlation between clinical features and expanded CAG repeats in the IT15 gene of 10 cases with juvenile-onset HD were studied carefully.  Results  Among 211 individuals carried expanded CAG repeats, 10 cases onset before 20 years of age. The predominant clinical manifestations were involuntary movement and cognitive impairment. The average age of onset was (12.50 ± 4.55) years, and the average CAG repeat number of IT15 gene was 63.70 ± 14.83. Pearson correlation analysis showed that the age of onset was significantly and negatively correlated with the CAG repeat number (r = - 0.865, P = 0.001). Conclusions  1) The juvenile?onset case of HD presented with different clinical features compared with adult - onset cases. The most common presentation is cognitive decline. 2) Analysis of CAG repeats of IT15 gene is necessary for the diagnosis of juvenile-onset case of HD with no family history. 3) The variability in age of onset is not completely explained by the effects of expanded CAG repeats of IT15 gene, which is more prominently for the juvenile?onset cases, therefore, it is
suggested that other factors may modulate the age of onset.

Key words: Huntington disease, Adolescent, Phenotype, Genes, Mutation, Pedigree