中文摘要：

目的：通过亚铁螯合酶（FECH）基因突变检测和核苷酸多态性分析确诊疾病,分析中国人群中红细胞生成性原卟啉病（EPP）的基因谱。创新点：通过FECH基因检测和多态性分析可精准诊断EPP这一罕见病,可减少漏诊误诊。另外,本研究扩充了中国EPP患者FECH基因突变谱。方法：选取北京协和医院就诊疑似EPP患者两例,采用聚合酶链反应（PCR）扩增FECH基因和5-氨基酮戊酸合成酶（ALAS2）基因并进行测序,同时在美国国立生物技术信息中心（NCBI）网站中比对基因突变情况,并行单核苷酸多态性（SNP）分析;通过荧光分光光度计检测其血浆中荧光激发峰值;检测血细胞内游离原卟啉浓度;临床评估皮肤对日光的光敏性。并对1名患者的FECH基因突变和SNP进行家系分析。结论：患者A的FECH基因cD NA中第973位碱基A缺失,造成病人的氨基酸序列从324位后发生框移突变;患者B的FECH基因cD NA中第1232位G〉T突变,造成病人411位的半胱氨酸转变为苯丙氨酸（图3）。结合两例患者皮肤光敏性损害（图1）、游离原卟啉增高、血浆荧光激发峰值在630~634 nm处出现（图2）和ALAS2基因未突变的特征,明确诊断为EPP。同时发现多个核苷酸突变,包括c.798 C〉G、c.921 A〉G、IVS1-23 C〉T、IVS3＋23 A〉G、IVS9＋35 C〉T和IVS3-48 T〉C（表1）。本研究通过基因鉴定和SNP分析,结合临床特征可精准诊断EPP这一罕见病,并扩充了中国EPP患者FECH基因突变谱。

英文摘要：

Erythropoietic protoporphyria（EPP）, an autosomal dominant disease, is caused by partial deficiency of ferrochelatase（FECH）, which catalyzes the terminal step of heme biosynthesis because of loss-of-function mutations in the FECH gene. To date, only a few cases have been described in Asia. In this study, we describe the clinical features of two Chinese patients with EPP, with diagnosis confirmed by the increase of free protoporphyrin in erythrocytes, detection of plasma fluorescence peak at 630–634 nm, and analysis of FECH gene mutations. Using gene scanning, we identified a small deletion in the FECH gene（c.973 delA） in one proband（patient A） and a pathogenic FECH mutation（c.1232 GT） in the other（patient B） and also observed some nucleotide variations（c.798 CG, c.921 AG, IVS1-23 CT, IVS3＋23 AG, IVS9＋35 CT, and IVS3-48 TC） in these patients. The family pedigree of patient A was then established by characterization of the genotype of the patient＇s relatives. We also analyzed the potential perniciousness of the missense mutation with bioinformatic software, Polyphen and Sift. In summary, Chinese EPP patients have similar manifestations to those of Caucasians, and identification of the Chinese FECH gene mutations expands the FECH genotypic spectrum and may contribute to genetic counseling.