关键词: 红细胞生成性原卟啉病;亚铁螯合酶;突变;剪接突变

Abstract:

Objective To investigate the FECH gene mutation in a Chinese family with erythropoietic protoporphyria, to explore the relationship between gene mutation and clinical manifestations so as to establish a basis for the genetic diagnosis and treatment of erythropoietic protoporphyria. Methods Clinical data on a Chinese family with typical EPP was collected. Peripheral blood was obtained from patients, unaffected individuals in the family and 50 unrelated human controls. Genomic DNA was extracted and PCR was performed to amplify the whole coding regions （exons 1 to 11） of FECH gene and their flanking intron sequences followed by direct sequencing to detect possible mutations. Results Based on clinical symptom and porphyrin levels, a diagnosis of erythropoietic protoporphyria was made in 3 family members. DNA fragments of expected size were amplified by PCR. Gene sequencing revealed a heterozygous mutation （IVS1 ＋ 1G ＞ C） in intron 1 of FECH gene in the proband, his sister and father, but not in unaffected family members or unrelated human controls. Also, an IVS1-23C/T polymorphism associated with low expression alleles was observed in intron 1 of FECH gene of the proband, his sister and mother. Conclusions A novel mutation in the donor splice site of intron 1 of FECH gene is first reported in a Chinese family with EPP; this mutation may lead to a deficiency of FECH gene and serve as a molecular basis of development of erythropoietic protoporphyria.