The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH
The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH
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DOI：
10.1038/ng809
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发表时间：
2002-01-01
期刊：
影响因子：
30.8
通讯作者：
Deybach, JC
中科院分区：
文献类型：
--
作者：
Gouya, L;Puy, H;Deybach, JC
红细胞生成性原红细胞增多症(EPP)是一种遗传性的血红素生物合成障碍，由铁络合酶(FECH，EC 4.99.1.1)(1，2)部分缺陷引起。EPP是一种常染色体显性遗传病(3)，具有不完全外显性(1)。通过单倍型分离分析，我们已经确定了一个内含子单核苷酸多态(SNP)，IVS3-48T/C，它调节了一个结构性异常受体剪接点的使用。异常剪接的mRNA被无义介导的衰退机制(NMD)降解，导致mRNA的稳态水平下降，并导致EPP表型表达所必需的额外的FECH酶缺陷。
Erythropoietic protoporphyria (EPP) is an inherited disorder of heme biosynthesis caused by a partial deficiency of ferrochelatase (FECH, EC 4.99.1.1)(1,2). EPP is transmitted as an autosomal dominant disorder(3) with an incomplete penetrance(1). Using haplotype segregation analysis, we have identified an intronic single nucleotide polymorphism (SNP), IVS3-48T/C, that modulates the use of a constitutive aberrant acceptor splice site. The aberrantly spliced mRNA is degraded by a nonsense-mediated decay mechanism (NMD), producing a decreased steady-state level of mRNA and the additional FECH enzyme deficiency necessary for EPP phenotypic expression.