Molecular basis of congenital erythropoietic porphyria: Mutations in the human uroporphyrinogen III synthase gene

Human MutationVolume 7, Issue 3 p. 187-192 Mutation UpdateFree Access Molecular basis of congenital erythropoietic porphyria: Mutations in the human uroporphyrinogen III synthase gene Weiming Xu, Weiming Xu Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029Search for more papers by this authorKenneth H. Astrin, Kenneth H. Astrin Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029Search for more papers by this authorRobert J. Desnick, Corresponding Author Robert J. Desnick Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029; Fax: 212-360-1809Search for more papers by this author Weiming Xu, Weiming Xu Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029Search for more papers by this authorKenneth H. Astrin, Kenneth H. Astrin Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029Search for more papers by this authorRobert J. Desnick, Corresponding Author Robert J. Desnick Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029; Fax: 212-360-1809Search for more papers by this author First published: 1996 https://doi.org/10.1002/(SICI)1098-1004(1996)7:3<187::AID-HUMU1>3.0.CO;2-8Citations: 30AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Congenital erythropoietic porphyria (CEP) is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of the fourth enzyme in the heme biosynthetic pathway, uroporphyrinogen III synthase (URO-synthase). To date, 17 mutations have been described including 11 missense, one nonsense, two mRNA splicing defects, one deletion and two coding region insertions. Most mutations have been identified in one or a few unrelated families with the exception of C73R and L4F which occurred in 29.6% and 9.3% of the 54 mutant alleles studied, respectively. Interestingly, analysis of the mutant alleles identified only 83% of the causative mutations, suggesting that about 20% of the mutations causing CEP lie elsewhere in the gene. Of note, mutation V82F, resulting from a G to T transversion of the last nucleotide of exon 4, caused both a missense mutation and an aberrantly spliced RNA transcript. Prokaryotic expression of the mutant URO-synthase alleles identified those with significant residual activity, thereby permitting genotype/phenotype predictions for this clinically heterogeneous disease. © 1996 Wiley-Liss, Inc. References Astrin KH, Warner CA, Yoo HW, Goodfellow PJ, Tsai SF, Desnick RJ (1991) Regional assignment of the human uroporphyrinogen III synthase (UROS) gene to chromosome 10q25-q26.3. Hum Genet 87: 18– 22. Barker DF, Shafer M, White R (1984) Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell 36: 131– 138. Battersby AR, Fookes CJR, Gustafson-Potter KE, McDonald E, Matcham GWJ (1982a) Biosynthesis of porphyrins and related macrocycles. Part 18. 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Xu W, Warner CA, Desnick RJ (1995a) Congenital erythropoietic porphyria: Identification and expression of ten mutations in the uroporphyrinogen III synthase gene. J Clin Invest 95: 905– 912. Xu W, Kozak AC, Desnick RJ (1995b) Uroporphyrinogen III synthase: Molecular cloning, nucleotide sequence, expression of a mouse full-length cDNA and its regional assignment to mouse chromosome 7. Genomics 26: 556– 562. Citing Literature Volume7, Issue31996Pages 187-192 ReferencesRelatedInformation