Novel mutations and phenotypic effect of the splice site modulator IVS3-48C in nine Swedish families with erythropoietic protoporphyria

Novel Null-Allele Mutations and Genotype-Phenotype Correlation in Argentinean Patients with Erythropoietic Protoporphyria

“…These findings are in agreement with the conclusion that the inheritance of a lowexpressed allele together with the mutation in the FECH gene are necessary for the clinical expression of this porphyria (4,13,14,16,(25)(26)(27).…”

“…Moreover, because the patient and his brother have inherited the low-expression haplotype from their mother, we can assume that the asymptomatic father in this family must have the haplotype -251A/A, IVS1-23C/C, IVS3-48T/T, and thus these individuals did not manifest the disease. This mutation, first described in a Finnish patient (22), has been also found in patients from France (28), Spain (26,29), Italy (30), Sweden (13), and China (31). Of the seven patients who carried the 343C>T mutation, only three suffered from liver disease (13,28,31).…”

“…This mutation, first described in a Finnish patient (22), has been also found in patients from France (28), Spain (26,29), Italy (30), Sweden (13), and China (31). Of the seven patients who carried the 343C>T mutation, only three suffered from liver disease (13,28,31). The reason for this finding is not yet well understood.…”

“…Thus, the presence of a T in the position IVS3-48 was shown to produce about 20% aberrantly spliced mRNA, whereas the presence of a C in this position leads to a higher presence, about 40%, of the abnormal mRNA, which would be easily degraded by the so-called nonsensemediated mRNA decay, producing a lower steady-state level of FECH mRNA (11,12). Although the inheritance of an IVS3-48C allele trans to the mutation explained the phenotypic expression in most families (4,(12)(13)(14), autosomal recessive inheritance can cause overt EPP in patients who do not have the low- expression allele. A small number of cases of recessive inheritance have been reported (15,16).…”

Identification of a ferrochelatase mutation in a Chinese family with erythropoietic protoporphyria

“…As we were unable to detect the mRNA transcripts from the ''null'' allele in the proband's derived EBV-B cells, we conclude that this mutation was responsible for nonsense-mediated decay of transcripts. The same Arg115X heterozygous mutation has previously been reported in several European countries, namely Finland [9], France [10], Italy [15], Sweden [16] and Spain [17], and it was suggested that this point mutation might have originated and congregated in central Europe. However, our identification of this Arg115X mutation in a Chinese patient questions this hypothesis.…”