Point mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria (Günther's disease).

Congenital erythropoietic porphyria (Günther's disease) is a rare disorder of heme biosynthesis inherited in an autosomal recessive fashion. The molecular abnormality responsible for the characteristic defect in uroporphyrinogen III synthase activity was investigated in two patients. For the first patient, complementary DNA was specifically amplified using the polymerase chain reaction and subsequently cloned and sequenced. Data obtained revealed the coexistence of two distinct point mutations: a T to C change in codon 73 (arginine in place of a cysteine) and a C to T change in codon 53 (leucine in place of a proline). The second case was studied by hybridization with allele specific oligonucleotides and was found to be homozygous for the same mutation in codon 53. These are the first mutations to be recognized in the uroporphyrinogen III synthase gene from congenital erythropoietic porphyria patients.