红细胞生成性原卟啉病一家系亚铁螯合酶基因突变检测

Mutation analysis of ferrochelatase gene in a pedigree with erythropoietic protoporphyria

目的通过对一例红细胞生成性原卟啉病家系亚铁螯合酶基因突变检测，探讨红细胞生成性原卟啉病的遗传特征。方法收集一例红细胞生成性原卟啉病家系中4例患者及3例表型正常者和50例无亲缘关系健康个体外周血标本，采用PCR扩增亚铁螯合酶基因全部11个外显子及侧翼序列并进行直接测序。结果先证者及其母亲、姐姐、表兄、外祖父中检测到一个新的剪接突变位点间隔序列（IVS）3＋1G—A，其外祖母和父亲未发现该突变；正常对照未发现此突变。先证者及其父亲、姐姐、表兄、外祖父两个单核苷酸多态性为IVS1—23T／C和IVS3—48C／T，而先证者的母亲与外祖母为IVS1—23C／C和IVS3—48T／T。结论发现红细胞生成性原卟啉病家系一个新的基因突变位点，该突变可能与两个低表达等位基因IVS1—23T和IVS3—48C共同导致红细胞生成性原卟啉病的临床表型。

Objective To characterize the inheritance of erythropoietic protoporphyria （EPP） by detecting the mutations of ferrochelatase （FECH） gene in a Chinese family with EPP. Methods Peripheral blood samples were obtained from 4 patients and 3 unaffected individuals in a family with EPP, as well as from 50 unrelated healthy human controls. PCR was performed to amplify all the 11 exons and flanking sequence of FECH gene followed by direct sequencing. Results A splicing mutation, i.e., IVS3＋1G→A, was identified in the proband as well as his symptomatic sister, cousin, grandfather and asymptomatic mother, but not in his asymptomatic father, grandmother, or unrelated healthy controls. The genotypes IVS1-23 T/C and IVS3-48 C/T were noted in the proband, his father, sister, cousin and grandfather, but absent in his mother or grandmother who carried IVS1-23 C/C and IVS3-48 T/T genotypes. Conclusions A novel splicing mutation is found in the FECH gene in a Chinese EPP family, which, together with two lowly expressed alleles IVS1-23T and IVS3- 48C, is likely to be responsible for the clinical phenotype of EPP in this family.