Wang X, Poh-Fitzpatrick M, Chen T, Malavade K, Carriero D, Piomelli S
Division of Pediatric Hematology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Biochim Biophys Acta. 1995 Jun 9;1271(2-3):358-62. doi: 10.1016/0925-4439(95)00059-d.
A systematic method was designed to screen a large population of patients with erythropoietic protoporphyria (EPP) for aberrant ferrochelatase RNA with skipped exons. The method utilizes the new junction sequence created by exon skipping as the probe to detect such RNA species. In 7 of 17 EPP families, an aberrant ferrochelatase RNA with one exon missing was observed. Two previously unreported splicing mutations were also identified in 2 EPP families. One was a G >> T transversion at the +1 position of the acceptor site of intron 8, causing exon 9 to be skipped during RNA splicing. Both the patient and her father were found to be heterozygous for this mutation. In another family, an A >> G transition at the +3 position of the donor site of intron 10 was identified, associated with exon 10 skipping during RNA splicing. Both the patient and her father were heterozygous for this mutation.
设计了一种系统方法，用于在大量红细胞生成性原卟啉症（EPP）患者中筛查具有外显子跳跃的异常铁螯合酶RNA。该方法利用外显子跳跃产生的新连接序列作为探针来检测此类RNA物种。在17个EPP家族中的7个家族中，观察到一种缺失一个外显子的异常铁螯合酶RNA。在2个EPP家族中还鉴定出两个以前未报道的剪接突变。一个是内含子8受体位点+1位置的G>>T颠换，导致RNA剪接过程中外显子9被跳过。发现患者及其父亲均为此突变的杂合子。在另一个家族中，鉴定出内含子10供体位点+3位置的A>>G转换，与RNA剪接过程中外显子10的跳跃有关。患者及其父亲均为此突变的杂合子。
