Spiegel R, La Spada A R, Kress W, Fischbeck K H, Schmid W
Institute of Medical Genetics, University of Zurich, Switzerland.
Hum Mutat. 1996;8(1):32-7. doi: 10.1002/(SICI)1098-1004(1996)8:1<32::AID-HUMU4>3.0.CO;2-R.
Expansion of trinucleotide repeats has now been associated with eight inherited diseases: X-linked spinal and bulbar muscular atrophy, two fragile X syndromes, myotonic dystrophy, Huntington's disease, spinocerebellar ataxia type I, dentatorubral pallidoluysian atrophy and Machado-Joseph disease. It has been shown that these expanded DNA repeats are unstable in number when transmitted from parents to offspring ("meiotic instability"), while somatic variation in repeat number has also been found in the fragile X syndrome and myotonic dystrophy. Moderate meiotic instability has been demonstrated in X-linked spinal and bulbar muscular atrophy (SBMA, Kennedy's disease). In order to determine if the expanded CAG repeat in SBMA also shows somatic instability, we compared different tissues from two patients with SBMA. We then examined the in vitro stability of the CAG repeat expansion by analyzing fibroblast cell cultures. Length comparison of expanded CAG repeats from all these materials clearly demonstrates that the CAG trinucleotide repeat in SBMA does not exhibit somatic variation.
如今，三核苷酸重复序列的扩增已与八种遗传性疾病相关联：X连锁脊髓和延髓性肌萎缩症、两种脆性X综合征、强直性肌营养不良症、亨廷顿舞蹈症、I型脊髓小脑共济失调、齿状核红核苍白球路易体萎缩症以及马查多-约瑟夫病。研究表明，这些扩增的DNA重复序列在从亲代传递给子代时数量不稳定（“减数分裂不稳定性”），而在脆性X综合征和强直性肌营养不良症中也发现了重复序列数量的体细胞变异。在X连锁脊髓和延髓性肌萎缩症（SBMA，肯尼迪病）中已证实存在中度减数分裂不稳定性。为了确定SBMA中扩增的CAG重复序列是否也表现出体细胞不稳定性，我们比较了两名SBMA患者的不同组织。然后，我们通过分析成纤维细胞培养物来检测CAG重复序列扩增的体外稳定性。对所有这些材料中扩增的CAG重复序列进行长度比较，清楚地表明SBMA中的CAG三核苷酸重复序列不表现出体细胞变异。
