Bonthron D T, Markham A F, Ginsburg D, Orkin S H
J Clin Invest. 1985 Aug;76(2):894-7. doi: 10.1172/JCI112050.
Deficiency of adenosine deaminase (ADA) is the cause of an autosomal recessive form of immunodeficiency. We sought to define, at a molecular level, the mutations responsible for ADA deficiency in the cell line GM-1715, derived from an immunodeficient patient. Full-length complementary DNA (cDNA) for ADA was synthesized and cloned from the cell line. Sequence analysis of the clones revealed a point mutation in codon 101 (CGG to CAG) that predicts an amino acid change from arginine to glutamine. Southern blot analysis, based on silent polymorphisms in the cDNA sequence, indicated that only one of the defective alleles of the GM-1715 line had been sequenced. The mutation that was identified appears to be responsible for the loss of function in this allele, since the predicted primary structure of the enzyme is otherwise entirely normal.
腺苷脱氨酶（ADA）缺乏是一种常染色体隐性免疫缺陷病的病因。我们试图在分子水平上确定源自一名免疫缺陷患者的细胞系GM - 1715中导致ADA缺乏的突变。从该细胞系中合成并克隆了ADA的全长互补DNA（cDNA）。对克隆进行的序列分析揭示了密码子101处的一个点突变（从CGG变为CAG），这预测了氨基酸从精氨酸变为谷氨酰胺。基于cDNA序列中的沉默多态性进行的Southern印迹分析表明，GM - 1715细胞系中只有一个缺陷等位基因被测序。所鉴定出的突变似乎是该等位基因功能丧失的原因，因为该酶的预测一级结构在其他方面完全正常。
