C73R IS A HOTSPOT MUTATION IN THE UROPORPHYRINOGEN III SYNTHASE GENE IN CONGENITAL ERYTHROPOIETIC PORPHYRIA

Congenital erythropoietic porphyria (CEP) results from profoundly defi cient activity of the fourth enzyme of the haeme biosynthetic pathway, uroporphyrinogen III synthase (UROIIIS). CEP is a rare, recessively i nherited disorder, and mutations in the UROIIIS gene detected in CEP p atients are heterogeneous. The notable exception to this rule is a sin gle missense mutation, designated C73R, which represents over 40% of a ll mutant UROIIIS alleles. In this study, we investigated three separa te families with CEP from different ethnic backgrounds. We performed h aplotype 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 studi ed. The results are consistent with the hypothesis that C73R is a hots pot mutation for CEP, and does not represent wide dispersion of a sing le ancestral mutant C73R allele.