Su T S, Beaudet A L, O'Brien W E
Nature. 1983 Feb 10;301(5900):533-4. doi: 10.1038/301533a0.
Citrullinaemia is a human inborn error of metabolism resulting from the deficiency of argininosuccinate synthetase. In a previous study of cultured skin fibroblasts from citrullinaemia patients, we showed that the presumed defects in DNA were not detectable by Southern blotting analysis, and that only 2 of 11 cell lines contained detectable enzyme antigen. All citrullinaemia cell lines contained hybridizable mRNA but slight size heterogeneity was noted. Here we report the extension of the analysis of the RNA using S1 nuclease mapping techniques. Among six cell lines examined, five showed an abnormality of mRNA detectable by S1 nuclease analysis. The data indicate that a minimum of three out of five non-consanguineous patients represent compound heterozygotes. The S1 nuclease detectable defects may represent deletions or rearrangements in the genomic DNA, or more probably represent examples of abnormal RNA splicing. The approach used here is useful for molecular analysis of genetic defects, for prenatal diagnosis, and for study of genetic variation.
瓜氨酸血症是一种由于精氨琥珀酸合成酶缺乏导致的人类先天性代谢缺陷。在之前一项对瓜氨酸血症患者培养的皮肤成纤维细胞的研究中，我们发现，通过Southern印迹分析无法检测到推测的DNA缺陷，并且在11个细胞系中只有2个含有可检测到的酶抗原。所有瓜氨酸血症细胞系都含有可杂交的mRNA，但注意到有轻微的大小异质性。在此，我们报告使用S1核酸酶作图技术对RNA分析的扩展。在所检测的6个细胞系中，5个显示通过S1核酸酶分析可检测到的mRNA异常。数据表明，5名非近亲患者中至少有3名是复合杂合子。S1核酸酶可检测到的缺陷可能代表基因组DNA中的缺失或重排，或者更可能代表异常RNA剪接的例子。这里使用的方法对于遗传缺陷的分子分析、产前诊断以及遗传变异研究很有用。
