PURPOSE: Hereditary angioedema (HAE) is a rare autosomal dominant life-threatening disease characterized by low levels of C1 inhibitor (type I HAE) or normal levels of ineffective C1 inhibitor (type II HAE), typically occurring as a consequence of a SERPING1 mutation. In some cases, a causal mutation remains undetected after using a standard molecular genetic analysis. RESULTS: Here we show a long methodological way to the final discovery of c.1029 + 384A > G, a novel deep intronic mutation in intron 6 which is responsible for HAE type I in a large family and has not been identified by a conventional diagnostic approach. This mutation results in de novo donor splice site creation and subsequent pseudoexon inclusion, the mechanism firstly described to occur in SERPING1 in this study. We additionally discovered that the proximal part of intron 6 is a region potentially prone to pseudoexon-activating mutations, since natural alternative exons and additional cryptic sites occur therein. Indeed, we confirmed the existence of at least two different alternative exons in this region not described previously. CONCLUSIONS: In conclusion, our results suggest that detecting aberrant transcripts, which are often low abundant because of nonsense-mediated decay, requires a modified methodological approach. We suggest SERPING1 intron 6 sequencing and/or tailored mRNA analysis to be routinely used in HAE patients with no mutation identified in the coding sequence.

• MeSH
• Child MeSH
• Adult MeSH
• Exons genetics   MeSH
• Hereditary Angioedema Types I and II genetics   MeSH
• Complement C1 Inhibitor Protein genetics   MeSH
• Introns genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• RNA Splice Sites genetics   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Mutation genetics   MeSH
• DNA Mutational Analysis methods   MeSH
• Pedigree MeSH
• Aged MeSH
• Protein Splicing genetics   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• Keywords
• SHR, genetika esenciální hypertenze,
• MeSH
• Ankyrin Repeat genetics   MeSH
• Gene Expression genetics   MeSH
• Genetic Predisposition to Disease MeSH
• Genotyping Techniques methods   MeSH
• Hypertension genetics   MeSH
• Disease Models, Animal MeSH
• Reverse Transcriptase Polymerase Chain Reaction utilization   MeSH
• Polymorphism, Genetic genetics   MeSH
• Rats, Inbred SHR genetics   MeSH
• Chromosomes, Mammalian genetics   MeSH
• Protein Splicing genetics   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH

• MeSH
• Genome, Fungal MeSH
• DNA Repair MeSH
• Gene Expression Regulation MeSH
• Software MeSH
• Protein Splicing MeSH
• Chromosomes, Artificial, Yeast MeSH

• Conspectus
• Biochemie. Molekulární biologie. Biofyzika
• NML Fields
• biologie
• lékařská informatika
• NML Publication type
• www dokumenty

• MeSH
• Adenomatous Polyposis Coli diagnosis   genetics   MeSH
• Genetic Testing methods   MeSH
• Genes, APC MeSH
• Nucleic Acid Heteroduplexes analysis   MeSH
• Humans MeSH
• Mutation MeSH
• Protein Splicing MeSH
• Check Tag
• Humans MeSH