Abstract |
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 in Escherichia 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.
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Authors | Amr A Shady, Brandon R Colby, Luis F Cunha, Kenneth H Astrin, David F Bishop, Robert J Desnick |
Journal | British journal of haematology
(Br J Haematol)
Vol. 117
Issue 4
Pg. 980-7
(Jun 2002)
ISSN: 0007-1048 [Print] England |
PMID | 12060141
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Uroporphyrinogen III Synthetase
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Topics |
- Amino Acid Sequence
- Base Sequence
- DNA Mutational Analysis
- Gene Deletion
- Gene Rearrangement
- Heterozygote
- Humans
- Molecular Sequence Data
- Mutation
- Mutation, Missense
- Porphyria, Erythropoietic
(enzymology, genetics)
- Uroporphyrinogen III Synthetase
(genetics, metabolism)
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