亨廷顿舞蹈症中三核苷酸重复序列长度与疾病进展
Trinucleotide repeat length and progression of illness in Huntington's disease.
作者信息
Kieburtz K, MacDonald M, Shih C, Feigin A, Steinberg K, Bordwell K, Zimmerman C, Srinidhi J, Sotack J, Gusella J
机构信息
Department of Neurology, University of Rochester Medical Center, New York 14642.
出版信息
J Med Genet. 1994 Nov;31(11):872-4. doi: 10.1136/jmg.31.11.872.
Abstract
The genetic defect causing Huntington's disease (HD) has been identified as an unstable expansion of a trinucleotide (CAG) repeat sequence within the coding region of the IT15 gene on chromosome 4. In 50 patients with manifest HD who were evaluated prospectively and uniformly, we examined the relationship between the extent of the DNA expansion and the rate of illness progression. Although the length of CAG repeats showed a strong inverse correlation with the age at onset of HD, there was no such relationship between the number of CAG repeats and the rate of clinical decline. These findings suggest that the CAG repeat length may influence or trigger the onset of HD, but other genetic, neurobiological, or environmental factors contribute to the progression of illness and the underlying pace of neuronal degeneration.
摘要
导致亨廷顿舞蹈症（HD）的基因缺陷已被确定为4号染色体上IT15基因编码区内三核苷酸（CAG）重复序列的不稳定扩增。我们对50例确诊为HD的患者进行了前瞻性、统一的评估，研究了DNA扩增程度与疾病进展速率之间的关系。尽管CAG重复序列的长度与HD发病年龄呈强烈负相关，但CAG重复序列的数量与临床衰退速率之间并无此关系。这些发现表明，CAG重复序列长度可能影响或引发HD的发病，但其他遗传、神经生物学或环境因素则影响疾病进展及神经元变性的潜在速度。
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