Brandt J, Bylsma F W, Gross R, Stine O C, Ranen N, Ross C A
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore MD 21287-7218, USA.
Neurology. 1996 Feb;46(2):527-31. doi: 10.1212/wnl.46.2.527.
We examined the relationship between length of the trinucleotide (CAG) repeat at IT-15 and clinical progression of Huntington's disease in 46 mildly to moderately affected patients over a 2-year interval. Patients were divided into those with short mutations (37 to 46 repeats; n = 25) and those with long mutations (> or = 47 repeats; n = 21). Patients with long repeat lengths had earlier age at onset and were younger and less functionally impaired than those with short repeats at the initial visit, but the groups did not differ in severity of neurologic or cognitive impairment. However, the long-repeat group displayed significantly greater decline in both neurologic and cognitive functioning over the 2-year follow-up period. The length of the CAG repeat correlated highly with age at onset (r = -0.72, p < 0.001) and was a strong predictor of decline in both neurologic and cognitive function. The mechanism of gene action, and the means by which longer expansions result in a more malignant disease process, remain to be elucidated.
我们研究了46例轻至中度亨廷顿病患者在两年间IT-15基因三核苷酸（CAG）重复序列长度与疾病临床进展之间的关系。患者被分为短突变组（37至46次重复；n = 25）和长突变组（≥47次重复；n = 21）。长重复序列长度的患者发病年龄较早，在初次就诊时比短重复序列患者更年轻且功能受损程度更低，但两组在神经或认知损害的严重程度上并无差异。然而，在两年的随访期内，长重复序列组在神经和认知功能方面的下降更为显著。CAG重复序列长度与发病年龄高度相关（r = -0.72，p < 0.001），并且是神经和认知功能下降的有力预测指标。基因作用机制以及更长的重复序列导致更恶性疾病进程的方式仍有待阐明。
