Sinnett D, Lavergne L, Melançon S B, Dallaire L, Potier M, Labuda D
Centre de Recherche Pédiatrique, Hôpital Sainte-Justine, Université de Montréal, Québec, Canada.
Hum Genet. 1988 Dec;81(1):4-8. doi: 10.1007/BF00283719.
Using human hypoxanthine-guanine phosphoribosyltransferase (HPRT) cDNA and an anonymous probe 36B-2, we examined the segregation of restriction fragment length polymorphism (RFLP) alleles with the Lesch-Nyhan phenotype in three affected families. Two families were informative. Five carriers of the mutation in one family and two potential carriers in the second were heterozygous for either one or both polymorphisms allowing for prenatal diagnosis. Southern blot patterns in patients from these three families indicated the absence of major structural alterations in the defective gene. Northern analysis using HPRT cDNA as a probe revealed no hybridizing RNA in one patient, whereas normal size mRNA was expressed at a very low level in the second and at a level comparable to normal in the third. These data are consistent with heterogeneity of Lesch-Nyhan genetic lesions resulting from point mutations or small DNA deletions or rearrangements, which may affect transcription, stability, or integrity of the HPRT message.
利用人类次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（HPRT）cDNA和一个无名探针36B - 2，我们在三个患病家庭中研究了限制性片段长度多态性（RFLP）等位基因与莱施 - 奈恩综合征表型的分离情况。有两个家庭提供了信息。在一个家庭中，五个突变携带者以及第二个家庭中的两个潜在携带者对于一种或两种多态性都是杂合的，这使得进行产前诊断成为可能。这三个家庭中患者的Southern印迹图谱表明缺陷基因中不存在主要的结构改变。使用HPRT cDNA作为探针进行的Northern分析显示，一名患者中没有杂交RNA，而在第二名患者中正常大小的mRNA以非常低的水平表达，在第三名患者中表达水平与正常相当。这些数据与由点突变、小的DNA缺失或重排导致的莱施 - 奈恩基因损伤的异质性一致，这些损伤可能会影响HPRT信息的转录、稳定性或完整性。
