Matsuyama Z, Izumi Y, Kameyama M, Kawakami H, Nakamura S
Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
J Med Genet. 1999 Jul;36(7):546-8.
The effect of CAT trinucleotide interruptions in the CAG trinucleotide repeats of the SCA1 gene on the age at onset of spinocerebellar ataxia type 1 (SCA1) was investigated. The number of CAG repeats in SCA1 was determined by polymerase chain reaction (PCR) analysis, and the presence of CAT interruptions was assessed on the basis of the sensitivity of the PCR products to the restriction endonuclease SfaNI, which recognises CAT trinucleotides. Only one in 17 expanded SCA1 alleles from 17 SCA1 patients was interrupted by CAT. The SfaNI sensitive SCA1 allele from this single patient contained 58 CAG repeats, which would predict an age at onset of SCA1 of 22.0 years, in contrast to the actual 50 years. In addition, the brain stem atrophy of this patient was mild compared with that of a patient with 52 uninterrupted CAG repeats. A sequence analysis showed that the repeat portion of the patient contained (CAG)45CATCAG CAT(CAG)10. From these results, we suggest that the age at onset of SCA1 is not determined by the total number of CAG repeats (58) but by the number of uninterrupted CAG repeats.
研究了SCA1基因CAG三核苷酸重复序列中CAT三核苷酸中断对1型脊髓小脑共济失调（SCA1）发病年龄的影响。通过聚合酶链反应（PCR）分析确定SCA1中CAG重复序列的数量，并根据PCR产物对识别CAT三核苷酸的限制性内切酶SfaNI的敏感性来评估CAT中断的存在情况。在17例SCA1患者的17个扩增SCA1等位基因中，只有1个被CAT中断。该单一患者的SfaNI敏感SCA1等位基因包含58个CAG重复序列，预计SCA1发病年龄为22.0岁，而实际发病年龄为50岁。此外，与一名具有52个不间断CAG重复序列的患者相比，该患者的脑干萎缩程度较轻。序列分析表明，该患者的重复部分包含（CAG）45CATCAG CAT（CAG）10。从这些结果来看，我们认为SCA1的发病年龄不是由CAG重复序列的总数（58个）决定的，而是由不间断CAG重复序列的数量决定的。
