Wang X, Poh-Fitzpatrick M, Taketani S, Chen T, Piomelli S
Division of Pediatric Hematology, Columbia University College of Physicians and Surgeons, New York, NY.
Biochim Biophys Acta. 1994 Jan 11;1225(2):187-90. doi: 10.1016/0925-4439(94)90077-9.
The DNA of 21 patients from 19 unrelated families with erythropoietic protoporphyria (EPP) were screened for the 6 ferrochelatase point mutations so far described. The mutation previously described by us (A >> T transversion at position -3 of the donor site of intron 10, causing exon 10 skipping) was detected in two additional unrelated EPP patients: in these patients, cDNA lacking exon 10 was also detected. The mutation described by Nakahashi et al. as responsible for exon 2 skipping (C >> T transition at position -23 of the acceptor site of intron 1), although also observed in some normal individuals, was invariably observed in all EPP patients tested and may thus play some role in the pathogenesis of EPP. Thus, it does not appear that this mutation is the primary mechanism underlying exon 2 skipping. None of the other four previously described mutations were detected. These data demonstrate the heterogeneity of the ferrochelatase locus and of the genetic defect in EPP.
对来自19个非亲缘性红细胞生成性原卟啉症（EPP）家庭的21例患者的DNA进行筛查，以检测迄今已报道的6种亚铁螯合酶点突变。我们之前描述的突变（内含子10供体位点-3处的A>>T颠换，导致外显子10跳跃）在另外2例非亲缘性EPP患者中被检测到：在这些患者中，还检测到了缺少外显子10的cDNA。Nakahashi等人描述的导致外显子2跳跃的突变（内含子1受体位点-23处的C>>T转换），尽管在一些正常个体中也有观察到，但在所有检测的EPP患者中均有发现，因此可能在EPP的发病机制中起一定作用。因此，该突变似乎不是外显子2跳跃的主要潜在机制。未检测到其他4种先前描述的突变。这些数据证明了亚铁螯合酶基因座和EPP遗传缺陷的异质性。
