Yang T P, Stout J T, Konecki D S, Patel P I, Alford R L, Caskey C T
Institute for Molecular Genetics and Howard Hughes Medical Institute, Houston, Texas.
Somat Cell Mol Genet. 1988 May;14(3):293-303. doi: 10.1007/BF01534590.
Molecular analysis of an unusual patient with the Lesch-Nyhan syndrome has suggested that the mutation is due to a partial HPRT gene duplication. We now report the cloning and sequencing of the mutant HPRT cDNA which shows the precise duplication of exons 2 and 3. This mutation is the result of an internal duplication of 16-20 kilobases of the gene. The structure of the mutant gene suggests that the duplication was not generated by a single unequal crossing-over event between two normal HPRT alleles. Growth of Epstein-Barr virus-transformed lymphoblasts from this patient in selective medium has permitted isolation of spontaneous HPRT+ revertants of this mutation. The reversion event involves a second major HPRT gene rearrangement where most or all of the duplicated portion of the mutant gene is deleted. The original mutation therefore has the potential for spontaneous somatic reversion. This may explain the relatively mild symptoms of the Lesch-Nyhan syndrome exhibited by this patient.
对一位患有莱施-奈恩综合征的特殊患者进行的分子分析表明，该突变是由于次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HPRT）基因部分重复所致。我们现在报告突变型HPRT互补DNA（cDNA）的克隆和测序情况，结果显示外显子2和3发生了精确重复。此突变是该基因内部16 - 20千碱基重复的结果。突变基因的结构表明，这种重复并非由两个正常HPRT等位基因之间的单一不等交换事件产生。在选择性培养基中培养该患者的爱泼斯坦-巴尔病毒转化的淋巴母细胞，使得能够分离出该突变的自发HPRT +回复体。回复事件涉及第二次主要的HPRT基因重排，其中突变基因的大部分或全部重复部分被删除。因此，原始突变具有自发体细胞回复的可能性。这或许可以解释该患者所表现出的相对较轻的莱施-奈恩综合征症状。
