Lamoril J, Boulechfar S, de Verneuil H, Grandchamp B, Nordmann Y, Deybach J C
Centre Français des Porphyries, Service de Biochimie, Hôpital Louis Mourier AP-HP, Colombes, France.
Biochem Biophys Res Commun. 1991 Dec 16;181(2):594-9. doi: 10.1016/0006-291x(91)91231-z.
The molecular basis of the ferrochelatase defect responsible for human Erythropoietic Protoporphyria (EPP), a usually autosomal dominant disease, was investigated in a family with an apparently homozygous patient. Two mutations of the ferrochelatase gene were identified by sequencing the proband's cDNA after in vitro amplification of the mRNA and subcloning of the amplified products. One mutation results from a G to T transition at nucleotide 163 which produces a glycine to cysteine substitution at amino-acid residue 55 (G-55-C). The other one was a G to A change at nucleotide 801, leading to a methionine to isoleucine substitution at amino-acid residue 267 (M-267-I). This EPP patient was then double heterozygous and as expected each of his parents carried one of the mutations. A second similar EPP patient was screened for these mutations with negative results, showing a genetic heterogeneity in EPP.
人类红细胞生成性原卟啉症（EPP）通常为常染色体显性疾病，在一个有明显纯合子患者的家族中，对导致该病的亚铁螯合酶缺陷的分子基础进行了研究。通过对先证者的mRNA进行体外扩增及对扩增产物进行亚克隆后，对其cDNA进行测序，确定了亚铁螯合酶基因的两个突变。一个突变是由于核苷酸163处的G到T转换，导致氨基酸残基55处的甘氨酸被半胱氨酸取代（G-55-C）。另一个突变是核苷酸801处的G到A变化，导致氨基酸残基267处的甲硫氨酸被异亮氨酸取代（M-267-I）。该EPP患者为双杂合子，正如所料，其父母各自携带其中一个突变。对另一名类似的EPP患者进行这些突变的筛查，结果为阴性，表明EPP存在遗传异质性。
