Four Novel UROD Gene Mutations Identified in Argentinean Patients with Familial Porphyria Cutanea Tarda

MEDINA NM; COLOMBO FEDERICO; ROSSETTI MARÍA VICTORIA; BATLLE, ALCIRA; PARERA VICTORIA ESTELA

Congreso; INTERNATIONAL CONGRESS ON PORPHYRINS AND PORPHYRIAS; 2013

Porphyria cutanea tarda (PCT), the most common porphyria, is caused by a decreased activity of uroporphyrinogen decarboxylase (UROD). The disease usually occurs in adulthood and is characterized by cutaneous photosensitivity, hyperpigmentation, skin fragility and hypertrichosis, caused by the overproduction of uroporphyrin and hepta- carboxylated porphyrins as a result of the enzyme deficiency. PCT is generally sporadic, but in about 20-30% of cases the disease is transmited as an autosomal dominant trait. This form of the disease is called familial PCT (F-PCT) and patients have about 50% reduced UROD activity in all tissues due to heterozygosity of mutations in the UROD gene. We have studied seven unrelated patients and 9 relatives and we have identified six mutations in the UROD gene, four of them were novel and two have been previously described. The novel mutations were: a missense mutation in the first base of the last codon of exon 5 (c.472 C>T), the deletion of cytosine 752 in exon 7 (c.752 del C), a 2 bp (GC) deletion in exon 10 (c.994_995 del GC) and a splicing mutation (c.213+1G>T) which alters the donor splicing site. In two infantile cases (8 and 11 years old), the pattern of urinary porphyrins did not correspond exactly to the typical PCT profiles, indicating that they may be cases of Hepatoerythropoyetic Porphyria (HEP). Molecular study confirmed PCT in both cases. Mutations g10insA and M165R, already found in Argentinean patients, were identified in one and two cases respectively, of the seven selected patients. Studies in the relatives, revealed one latent PCT, two normal subjects and confirmed the familial mutation in the other six. Genetic study allows us to detect four novel mutations in the URO-D gene, to get the differential diagnostic in cases of atypic biochemical results and to obtain the familial presymptomatic diagnosis to avoid exposure to triggering factors and therefore the Porphyria clinical signs manifestation.