Parera V.E.1, Koole R.2, Batlle A.1, De Rooij F.W.M.2
1CIPYP, Buenos Aires, Argentina, 2Lab. Internal Medicine II, University Hospital, Rotterdam, The Netherlands
Hereditary coproporphyria (HCP) is a metabolic disease produced by a deficiency in coproporphyrinogen III oxidase (CPO), the sixth enzyme of heme pathway, first reported in 1955. Clinically, HCP is a mixed porphyria and patients may present abdominal pain and/or cutaneous symptoms. Biochemically, diminished activity of CPO produces accumulation of coproporphyrin both in urine and faeces and during attacks, excess urinary porphobilinogen and delta-aminolevulinic acid excretion is found. The human CPO gene contains seven exons and spans 14 kb of genomic DNA. The cDNA has an open reading frame of 1062 bp encoding a protein of 354 amino acids and the mature protein consists of 323 amino acid residues. So far, 33 different mutations and 8 polymorphisms have been characterized in the human CPO gene: 23 nucleotide substitutions, 3 splicing mutations, 4 small deletions, 2 small insertions and 1 gross deletion. Genomic DNA was isolated from peripheral blood samples from 4 HCP Argentinean patients and their available relatives using InstaGene Whole Blood Kit (Bio Rad). The 7 exons of CPO gene, including the flanking intronic regions were amplified by the polymerase chain reaction and sequenced using a DNA sequencing kit (Applied Biosystems), reactions were run on an ABI PRISM 310 Genetic Analyzer (Perkin Elmer). In the CPO gene of four unrelated families we have detected 4 novel mutations: one point mutation g/a in intron 6 at position +5 of the donor site of splicing (IVS6 +5g/a), one point mutation in exon 6 changing a tyrosine (TAT) by a cysteine (TGT) (Y392C), one point mutation a/c in the acceptor site of splicing in intron 2 (IVS2-2 a/c) and the deletion of one C in exon 1 (279delC). This is the first genetic study in HCP Argentinean patients and these results are showing again, the genetic heterogeneity of the porphyrias.