Haploinsufficiency due to deletion within the 3'-UTR of C1-INH-gene associated with hereditary angioedema.
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.
Laimer
Martin
M
Division of Molecular Dermatology, Department of Dermatology, Paracelsus Private Medical University Salzburg, Salzburg, Austria.
Klausegger
Alfred
A
Aberer
Werner
W
Oender
Kamil
K
Steinhuber
Mathias
M
Lanschuetzer
Christoph M
CM
Wally
Verena
V
Hintner
Helmut
H
Bauer
Johann W
JW
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
D020413:3' Untranslated Regions; D003174:Complement C1 Inactivator Proteins