Congenital erythropoietic porphyria: identification and expression of eight novel mutations in the uroporphyrinogen III synthase gene.
Congenital erythropoietic porphyria: identification and expression of eight novel mutations in the uroporphyrinogen III synthase gene.
复制标题
先天性红细胞生成性卟啉症：尿卟啉原 III 合酶基因中八个新突变的鉴定和表达。
DOI：
10.1046/j.1365-2141.2002.03558.x
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发表时间：
2002
影响因子：
6.5
通讯作者：
Desnick,RobertJ
中科院分区：
文献类型：
--
作者：
Shady,AmrA;Colby,BrandonR;Cunha,LuisF;Astrin,KennethH;Bishop,DavidF;Desnick,RobertJ
Mutations in the uroporphyrinogen III synthase (URO‐synthase) gene cause congenital erythropoietic porphyria (CEP), an autosomal recessive inborn error of haem biosynthesis. Molecular analysis of the URO‐synthase gene in seven unrelated CEP patients revealed eight novel mutations. These included four missense mutations (A69T, E81D, G188W and I219S), a deletion (21delG), two insertions (398insG and 672ins28) and one complex mutation (627del6ins39), as well as three previously reported mutations, C73R, T228M, and −86C→A. When the four novel missense mutations were expressed inEscherichia coli,only E81D expressed significant enzymatic activity (30% of expressed wild‐type activity), which was thermolabile. In addition, reverse transcription polymerase chain reaction studies demonstrated that E81D, which altered the penultimate nucleotide in exon 4, impaired splicing and caused about 85% exon 4 skipping. The identification and expression of these mutations provided genotype–phenotype correlations and further evidence of the molecular heterogeneity underlying this erythropoietic porphyria.
