Lamont P J, Davis M B, Wood N W
University Department of Clinical Neurology, Institute of Neurology, London, UK.
Brain. 1997 Apr;120 ( Pt 4):673-80. doi: 10.1093/brain/120.4.673.
Fifty-six patients with a clinical diagnosis of Friedreich's ataxia were investigated for the GAA trinucleotide repeat expansion recently found within the gene X25 on chromosome 9. All 56 were found to be homozygous for the expansion, with all but two patients having alleles of differing sizes. The expansion size ranged from 2 to 5 kb, with normal alleles around 1.5 kb. Sizing of the single copy of the expansion in eight sets of parents revealed marked instability in the transmission of the expansion, with both increases and decreases in allele size seen. In Friedreich's ataxia patients there was a significant inverse correlation seen between the average of the two expansions sizes and age of onset of symptoms. The GAA repeat expansion was found in the homozygous state in atypical cases of Friedreich's ataxia, such as older age of onset, preservation of lower limb reflexes and cardiac presentations. In three families the father had onset of spinocerebellar ataxia as an adult, and in two the possibility of partial expression in heterozygote carrier fathers has been raised. More importantly, the history of an ataxic syndrome in a parent does not exclude the diagnosis of Friedreich's ataxia in the offspring, and tests for the expansion should be carried out. The third family with an affected father conforms to previously described 'pseudodominant' inheritance.
对56例临床诊断为弗里德赖希共济失调的患者进行了研究，以检测最近在9号染色体上的X25基因中发现的GAA三核苷酸重复序列扩增情况。所有56例患者均被发现为该扩增的纯合子，除2例患者外，其余患者的等位基因大小均不同。扩增大小范围为2至5 kb，正常等位基因约为1.5 kb。对八组父母中扩增的单拷贝进行大小测定，结果显示扩增在传递过程中存在明显的不稳定性，等位基因大小既有增加也有减少。在弗里德赖希共济失调患者中，两个扩增大小的平均值与症状发作年龄之间存在显著的负相关。在弗里德赖希共济失调的非典型病例中，如发病年龄较大、下肢反射保留和心脏表现等，发现了GAA重复序列扩增的纯合状态。在三个家庭中，父亲在成年后出现脊髓小脑共济失调，在两个家庭中，杂合子携带者父亲存在部分表达的可能性。更重要的是，父母有共济失调综合征病史并不排除后代患弗里德赖希共济失调的诊断，应进行扩增检测。第三个父亲患病的家庭符合先前描述的“假显性”遗传。
