Filla A, De Michele G, Cavalcanti F, Pianese L, Monticelli A, Campanella G, Cocozza S
Department of Neurology, Federico II University, Naples, Italy.
Am J Hum Genet. 1996 Sep;59(3):554-60.
Friedreich ataxia (FA) is associated with the expansion of a GAA trinucleotide repeat in the first intron of the X25 gene. We found both alleles expanded in 67 FA patients from 48 Italian families. Five patients from three families were compound heterozygotes with expansion on one allele and an isoleucine-->phenylalanine change at position 154 on the other one. We found neither expansions nor point mutations in three patients. The length of FA alleles ranged from 201 to 1,186 repeat units, with no overlap with the normal range, and showed a negatively skewed distribution with a peak between 800 and 1,000 repeats. The FA repeat showed meiotic instability with a median variation of 150 repeats. The lengths of both larger and smaller alleles in each patient inversely correlated with age at onset of the disorder. Smaller alleles showed the best correlation, accounting for approximately 50% of the variation of age at onset. Mean allele length was significantly higher in patients with diabetes and in those with cardiomyopathy.
弗里德赖希共济失调（FA）与X25基因第一内含子中GAA三核苷酸重复序列的扩增有关。我们在来自48个意大利家庭的67例FA患者中发现两个等位基因均发生了扩增。来自三个家庭的5例患者为复合杂合子，一个等位基因发生扩增，另一个等位基因在第154位发生异亮氨酸→苯丙氨酸的改变。我们在3例患者中既未发现扩增也未发现点突变。FA等位基因的长度范围为201至1186个重复单位，与正常范围无重叠，呈负偏态分布，峰值在800至1000个重复之间。FA重复序列表现出减数分裂不稳定性，中位数变化为150个重复。每位患者中较大和较小等位基因的长度与疾病发病年龄呈负相关。较小的等位基因相关性最佳，约占发病年龄变异的50%。糖尿病患者和心肌病患者的平均等位基因长度显著更高。
