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.