Wang X, Poh-Fitzpatrick M, Piomelli S
Division of Pediatric Hematology, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Biochim Biophys Acta. 1994 Oct 21;1227(1-2):25-7. doi: 10.1016/0925-4439(94)90101-5.
An aberrant ferrochelatase mRNA lacking exon 7 was found in a patient with erythropoietic protoporphyria (EPP). The exon 7 skipping appears to result from a G >> A transition at position +5 of the donor site of intron 7 of the ferrochelatase gene. The patient is heterozygous for the mutation. Since the patient's paternal half-brother (not available for testing) also has clinically obvious EPP, their father appeared to be the source of the mutant allele. The father was in fact found to be a carrier of the same mutation and his ferrochelatase activity was 35% of normal; however, he is asymptomatic, with only a slightly elevated erythrocyte protoporphyrin level. These findings confirm that the observed mutation is responsible for the defect. The variability in clinical expression of EPP probably reflects the great heterogeneity of the ferrochelatase gene defects and the contribution of additional exogenous and endogenous inducers of latent disease.
在一名红细胞生成性原卟啉病（EPP）患者中发现了一种缺少第7外显子的异常铁螯合酶mRNA。第7外显子的跳跃似乎是由铁螯合酶基因内含子7供体位点+5处的G>>A转换引起的。该患者为该突变的杂合子。由于患者同父异母的兄弟（无法进行检测）也有临床明显的EPP，他们的父亲似乎是突变等位基因的来源。事实上，父亲被发现是同一突变的携带者，其铁螯合酶活性为正常水平的35%；然而，他没有症状，只有红细胞原卟啉水平略有升高。这些发现证实了观察到的突变是导致缺陷的原因。EPP临床表型的变异性可能反映了铁螯合酶基因缺陷的高度异质性以及潜在疾病的其他外源性和内源性诱导因素的作用。
