title: A Novel Mutation in the FECH Gene in a Czech Family with Erythropoietic Protoporphyria and a Population Study of IVS3-48C Variant Contributing to the Disease.
abstract: Erythropoietic protoporphyria (EPP), a chronic erythropoietic porphyria, is characterized by excess accumulation of protoporphyrin, particularly in erythroid cells. EPP inheritance is complex, almost always associated with two molecular defects. In most EPP patients, clinical expression requires coinheritance of a private ferrochelatase (FECH) mutation trans- to a hypomorphic FECH*IVS3-48C allele. This leads to a decrease of FECH activity below the critical threshold. This is characterized by cutaneous photosensitivity in early childhood such as itching, burning, swelling and redness in sun-exposed areas. Hepatic failure occurs in some patients (about 1-10 % of EPP patients), which may necessitate liver transplantation. We investigated a Czech family with two patients with manifested EPP in four generations. We found a novel mutation, c.84G >A, in the FECH gene in four individuals including proband and his mother (G84A transition in exon 2; p.W28*). Both clinically manifested probands inherited the hypomorphic IVS3-48C allele as well, while two clinically latent individuals with FECH mutation did not. To address the question whether the relatively low incidence of EPP in the Czech Republic might be due to lower frequency of the IVS3-48C allele, we screened for the frequency of the low expression allele in a control Czech (West Slaves) Caucasian population. Such study has not been performed in any Slavic population. Among 312 control individuals, there were no IVS3-48C/C (c.68-23C-T) homozygotes; 35 IVS3-48C/T heterozygous individuals were detected. The frequency of IVS3-48C allele was thus found to be 5.5 % in the Czech population, comparable to most West Caucasian populations.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
authors.forename: M S
authors.initials: MS
authors.lastname: Farrag
authors.affiliation: Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Kučerová
authors.affiliation: Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Šlachtová
authors.affiliation: Institute of Biology and Genetics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
authors.forename: O
authors.initials: O
authors.lastname: Šeda
authors.affiliation: Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Šperl
authors.affiliation: Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Martásek
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D053898:Biosynthetic Pathways / Q000235:genetics; D018153:Czech Republic; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000378:metabolism; D005190:Family; D005260:Female; D005294:Ferrochelatase / Q000737:chemistry / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006418:Heme / Q000096:biosynthesis; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D046351:Protoporphyria, Erythropoietic / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D011524:Protoporphyrins / Q000097:blood
chemical_list: D011524:Protoporphyrins; D006418:Heme; D004247:DNA; D005294:Ferrochelatase