Rossi A M, Thijssen J C, Tates A D, Vrieling H, Natarajan A T, Lohman P H, van Zeeland A A
MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University, The Netherlands.
Mutat Res. 1990 Aug;244(4):353-7. doi: 10.1016/0165-7992(90)90084-w.
The spectrum of DNA sequence alterations in the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene of HPRTase-deficient T-lymphocytes isolated from the blood of healthy male donors was determined and compared with the spectrum found in patients suffering from genetic diseases (Lesch-Nyhan syndrome or gouty arthritis) associated with a mutation in the same gene. Most of the T-cell mutants still produced hprt mRNA which was converted into cDNA and used for DNA sequence analysis after amplification using the polymerase chain reaction (PCR). In 39% of the 31 analyzed T-cell mutants of normal donors 1 or 2 exons were completely or partially deleted from hprt mRNA, probably because of a mutation in a splice acceptor site. Among patients suffering from the Lesch-Nyhan syndrome or gouty arthritis, the class of splice mutations amounts only to 7%. These data suggest that carriers of splice mutations often do not show the characteristics of HPRTase deficiency associated with these genetic diseases, because correctly spliced hprt mRNA is still produced at a low level.
对从健康男性献血者血液中分离出的次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（hprt）基因缺陷的T淋巴细胞中的DNA序列改变谱进行了测定，并与在患有与同一基因突变相关的遗传疾病（莱施 - 奈恩综合征或痛风性关节炎）的患者中发现的谱进行了比较。大多数T细胞突变体仍产生hprt mRNA，该mRNA被转化为cDNA，并在使用聚合酶链反应（PCR）扩增后用于DNA序列分析。在31个分析的正常供体的T细胞突变体中，39%的突变体中hprt mRNA的1个或2个外显子完全或部分缺失，这可能是由于剪接受体位点的突变。在患有莱施 - 奈恩综合征或痛风性关节炎的患者中，剪接突变的类别仅占7%。这些数据表明，剪接突变的携带者通常不表现出与这些遗传疾病相关的次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶缺乏的特征，因为仍会以低水平产生正确剪接的hprt mRNA。
