title: C73R is a hotspot mutation in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria.
abstract: Congenital erythropoietic porphyria (CEP) results from profoundly deficient activity of the fourth enzyme of the haeme biosynthetic pathway, uroporphyrinogen III synthase (UROIIIS). CEP is a rare, recessively inherited disorder, and mutations in the UROIIIS gene detected in CEP patients are heterogeneous. The notable exception to this rule is a single missense mutation, designated C73R, which represents over 40% of all mutant UROIIIS alleles. In this study, we investigated three separate families with CEP from different ethnic backgrounds. We performed haplotype analysis using two microsatellite markers that closely flank the UROIIIS gene on chromosome 10q24, spanning a region of 4 cM on the GB4 linkage panel. Haplotype analysis revealed the occurrence of C73R on different haplotypes in four out of four disease chromosomes studied. The results are consistent with the hypothesis that C73R is a hotspot mutation for CEP, and does not represent wide dispersion of a single ancestral mutant C73R allele.
authors.affiliation: Department of Dermatology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: J
authors.initials: J
authors.lastname: Frank
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: H M
authors.initials: HM
authors.lastname: Lam
authors.forename: V M
authors.initials: VM
authors.lastname: Aita
authors.forename: F K
authors.initials: FK
authors.lastname: Jugert
authors.forename: G
authors.initials: G
authors.lastname: Goerz
authors.forename: H F
authors.initials: HF
authors.lastname: Merk
authors.forename: M B
authors.initials: MB
authors.lastname: Poh-Fitzpatrick
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D001483:Base Sequence; D002879:Chromosomes, Human, Pair 10; D017931:DNA Primers; D005260:Female; D006580:Genetic Carrier Screening; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D017092:Porphyria, Erythropoietic / Q000235:genetics*; D014576:Uroporphyrinogen III Synthetase / Q000235:genetics*
chemical_list: D017931:DNA Primers; D014576:Uroporphyrinogen III Synthetase