Hsieh M, Lin S J, Chen J F, Lin H M, Hsiao K M, Li S Y, Li C, Tsai C J
Department of Life Sciences, Chung Shan Medical and Dental College, Taichung, Taiwan, ROC.
J Neurol. 2000 Aug;247(8):623-9. doi: 10.1007/s004150070131.
Spinocerebellar ataxia (SCA) type 7 is an autosomal dominant disorder characterized by neural loss, mainly in the cerebellum and regions of the brainstem and particularly the inferior olivary complex. This neurodegeneration disease is associated with expansion of unstable CAG repeats within the 5'-translated region of the SCA7 gene, located on chromosome 3p. We conducted a local survey of the normal population and candidate patients for the analysis of the CAG repeats in the SCA7 gene. The distributions of the CAG repeat units of SCA7 gene in the normal population in Taiwan were established in this study by using the radioactive genomic polymerase chain reaction (PCR). The normal range of CAG repeats is from 6 to 17 repeats, with the more common being around 8-13 repeats. The range is narrower than that reported for other ethnic groups (7-35 CAGs). Meanwhile, by the use of a combination of PCR and Southern blot analysis, one SCA7 family was identified and is reported here. A marked instability of the CAG repeat number during transmission from father to son (41 vs. 100) was observed in the SCA7 family. Clinical anticipation is significant in this family including an infantile case, who was found to have nystagmus from the age of 1 month. To date, the SCA7 mutation has been detected in one of 73 families with autosomal dominant cerebellar ataxia phenotypes, which is about 1.4% of the ataxia families referred to us, compared to 1.4% SCA1, 9.6% SCA2, and 27.3% SCA3/Machado-Joseph disease in our collection. In addition, we demonstrate that the PCR-based Southern blot analysis, with the advantages of sensitivity of PCR and specificity of Southern blot, is a reliable diagnostic method for SCA7 mutation screening. The molecular analysis technique makes possible the quick and accurate diagnosis of SCA7 patients and in the future will hopefully be applied to prenatal screening for SCA7 families.
7型脊髓小脑共济失调（SCA7）是一种常染色体显性疾病，其特征为神经细胞丧失，主要发生在小脑、脑干区域，尤其是下橄榄核复合体。这种神经退行性疾病与位于3号染色体短臂上的SCA7基因5'-翻译区不稳定的CAG重复序列的扩增有关。我们对正常人群和候选患者进行了本地调查，以分析SCA7基因中的CAG重复序列。本研究通过放射性基因组聚合酶链反应（PCR）确定了台湾正常人群中SCA7基因CAG重复单位的分布。CAG重复序列的正常范围是6至17次重复，最常见的是8 - 13次重复。该范围比其他种族报道的范围（7 - 35个CAG）更窄。同时，通过PCR和Southern印迹分析相结合的方法，鉴定出一个SCA7家系并在此报告。在该SCA7家系中观察到从父亲传给儿子时CAG重复数的显著不稳定性（41对100）。该家系中临床遗传早现现象明显，包括一名婴儿病例，该婴儿从1个月大时就被发现有眼球震颤。迄今为止，在73个具有常染色体显性小脑共济失调表型的家系中检测到1个SCA7突变家系，约占转介给我们的共济失调家系的1.4%，而在我们收集的家系中，SCA1为1.4%，SCA2为9.6%，SCA3/马查多-约瑟夫病为27.3%。此外，我们证明基于PCR的Southern印迹分析具有PCR的敏感性和Southern印迹的特异性，是一种可靠的SCA7突变筛查诊断方法。这种分子分析技术使快速准确诊断SCA7患者成为可能，未来有望应用于SCA7家系的产前筛查。
