title: Haploinsufficiency due to deletion within the 3'-UTR of C1-INH-gene associated with hereditary angioedema.
abstract: OBJECTIVE
  Sequences within the non-coding 3'UTR (untranslated region) of genes were reported to be involved in the regulation of gene expression by modifying pathways of (co)transcription, post-transcriptional processing and RNA transport. However, direct biological evidence (i.e., knock-out models) is sparse. This report intends to correlate the first reported alteration within the 3'UTR of the C1 inhibitor (C1-INH) gene with clinical presentation of hereditary angioedema (HAE).
  
  
  RESULTS
  Direct sequencing of genomic DNA revealed in all affected members of a family suffering from HAE a heterozygous 155 bp deletion 100 bp downstream of the physiological stop-codon in exon 8. A substantial reduction of both mRNA as well as C1-INH protein expression was revealed by RT-PCR and nephelometry, respectively.
  
  
  CONCLUSIONS
  We suppose that the mutation within the 3'UTR interferes with integral pathways of gene expression leading to pathogenic haploinsufficiency in this family.
authors.affiliation: Division of Molecular Dermatology, Department of Dermatology, Paracelsus Private Medical University Salzburg, Salzburg, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Laimer
authors.forename: Alfred
authors.initials: A
authors.lastname: Klausegger
authors.forename: Werner
authors.initials: W
authors.lastname: Aberer
authors.forename: Kamil
authors.initials: K
authors.lastname: Oender
authors.forename: Mathias
authors.initials: M
authors.lastname: Steinhuber
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Lanschuetzer
authors.forename: Verena
authors.initials: V
authors.lastname: Wally
authors.forename: Helmut
authors.initials: H
authors.lastname: Hintner
authors.forename: Johann W
authors.initials: JW
authors.lastname: Bauer
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000799:Angioedema / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D003174:Complement C1 Inactivator Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017384:Sequence Deletion
chemical_list: D020413:3' Untranslated Regions; D003174:Complement C1 Inactivator Proteins