title: Seven novel point mutations in the uroporphyrinogen decarboxylase (UROD) gene in patients with familial porphyria cutanea tarda (f-PCT).
abstract: In this work, we describe seven novel molecular defects in the uroporphyrinogen decarboxylase gene responsible for familial porphyria cutanea tarda in Italian subjects with reduced erythrocyte URO-D activity. Four of these molecular abnormalities (R142Q, L161Q, S219F, P235S) are missense mutations, one (Q206X) is a nonsense mutation, one (IVS8-1 G>C) is a splicing defect causing the exon 9 deletion and one (1107 G>A) is located in the 3' untranslated region of UROD gene. All the amino acid substitutions fall in conserved regions in several organisms suggesting an important role in catalysis or in the protein structure stabilization. Three of these mutations have been detected in more than one subject. These results suggest a molecular heterogeneity at the UROD locus in Italian PCT patients although recurrent mutations have been identified.
authors: Centro Anemie Congenite, Ospedale Maggiore Policlinico IRCCS, Dipartimento di Medicina Interna, University of Milan, Italy. maria.cappellini@unimi.it
authors: M D
authors: MD
authors: Cappellini
authors: F
authors: F
authors: Martinez di Montemuros
authors: D
authors: D
authors: Tavazzi
authors: S
authors: S
authors: Fargion
authors: A
authors: A
authors: Pizzuti
authors: A
authors: A
authors: Comino
authors: T
authors: T
authors: Cainelli
authors: G
authors: G
authors: Fiorelli
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002384:Catalysis; D017124:Conserved Sequence / Q000235:genetics; D004252:DNA Mutational Analysis; D004795:Enzyme Stability / Q000235:genetics; D004912:Erythrocytes / Q000201:enzymology* / Q000473:pathology; D005091:Exons / Q000235:genetics; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D017354:Point Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D017119:Porphyria Cutanea Tarda / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics; D014575:Uroporphyrinogen Decarboxylase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D014575:Uroporphyrinogen Decarboxylase