Gunaratne P H, Richards C S
Baylor DNA Diagnostic Laboratory, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Genet Test. 1997;1(4):275-8. doi: 10.1089/gte.1997.1.275.
We estimated the relative contributions of known ataxia genes (SCA1, 2, 3, 6, 7 and X25) in the patient population sent to our DNA diagnostic laboratory for diagnostic testing. Approximately 28% of these patients had an abnormal triplet repeat expansion in one of these ataxia genes (3% for SCA1, 8% for SCA2, 11% for SCA3/MJD, 2% for SCA6, 3% for SCA7, and 1.5% for X25). The lack of abnormal repeat expansions in the majority of ataxis patients tested suggests that the molecular defects associated with most ataxia cases are currently undetermined and that this population includes both familial and sporadic cases. In contrast, of the patients submitted for genetic testing for Friedrich's ataxia (FRDA), 44% (69/157) showed at least one expansion in the X25 gene, indicating that FRDA accounts for a significant proportion of the recessively inherited ataxias and appears to have a high rate of accurate clinical diagnosis. On the basis of our DNA studies, we propose a comprehensive and efficient approach for molecular analysis of ataxia patients.
我们评估了已知共济失调基因（脊髓小脑共济失调1型、2型、3型、6型、7型和X25）在送往我们DNA诊断实验室进行诊断检测的患者群体中的相对贡献。这些患者中约28%在这些共济失调基因中的某一个存在异常三联体重复扩增（脊髓小脑共济失调1型为3%，脊髓小脑共济失调2型为8%，脊髓小脑共济失调3型/马查多-约瑟夫病为11%，脊髓小脑共济失调6型为2%，脊髓小脑共济失调7型为3%，X25为1.5%）。大多数接受检测的共济失调患者缺乏异常重复扩增，这表明与大多数共济失调病例相关的分子缺陷目前尚未明确，并且该群体包括家族性和散发性病例。相比之下，在提交进行弗里德赖希共济失调（FRDA）基因检测的患者中，44%（69/157）在X25基因中至少有一次扩增，这表明FRDA在隐性遗传性共济失调中占很大比例，并且似乎具有较高的准确临床诊断率。基于我们的DNA研究，我们提出了一种针对共济失调患者的全面且高效的分子分析方法。
