Related Experiment Video
Updated: Aug 13, 2026
Microinjection of CRISPR/Cas9 Protein into Channel Catfish, Ictalurus punctatus, Embryos for Gene Editing
Published on: January 20, 2018
Normal C1 inhibitor mRNA expression level in type I hereditary angioedema patients: newly found C1 inhibitor gene
1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Insights
Researchers identified novel mutations and gene deletions in C1 esterase inhibitor (C1INH) associated with hereditary angioedema (HAE). Some HAE cases may stem from post-translational defects, not just gene mutations.
Area of Science:
- Genetics
- Immunology
- Molecular Biology
Background:
- C1 esterase inhibitor (C1INH) is crucial for the complement cascade's classical pathway.
- Mutations in the C1INH gene lead to hereditary angioedema (HAE) types I and II due to reduced antigenic or functional C1INH levels.
Purpose of the Study:
- Identify novel mutations in the C1INH gene in HAE patients.
- Evaluate C1INH gene expression levels in HAE patients.
Main Methods:
- Direct sequencing of genomic DNA from HAE patients and family members.
- Southern blotting for large genomic rearrangements in one family.
- Real-time quantitative PCR for C1INH mRNA expression analysis.
Main Results:
- Discovered four exonal and four intronic mutations in C1INH, including Gly345Arg and a splice site mutation.
- Identified a large gene deletion in a family without detectable sequencing mutations.
- C1INH mRNA levels were not significantly different in HAE patients compared to controls.
Conclusions:
- Novel exonal mutations and a large gene deletion in C1INH are linked to HAE phenotypes.
- Normal C1INH mRNA with reduced protein levels suggests post-translational defects in some HAE cases.
Background:
C1 esterase inhibitor (C1INH) plays a key role in the classical pathway of the complement cascade. Mutations in this gene cause a decreased level of antigenic (type I hereditary angioedema, HAE) or functional (type II HAE) C1INH.
Objective:
To find novel mutations in C1INH and evaluate the expression of C1INH gene in HAE patients.
Methods:
Direct sequencing mutation analysis was performed for genomic DNA from three unrelated families (14 HAE patients and 18 family members). Genomic DNA from one family was also analyzed for larger genomic rearrangements, using Southern blotting analysis. We used real-time quantitative polymerase chain reaction (PCR) to evaluate C1INH mRNA expression level.
Results:
Four mutations in exons (2,311 T-->C, 14,034 G-->A, 16,830 G-->A, and 16,979-16,980 G insertion) and four in introns (738 G-->A, 8,531 A-->G, 14,254 A-->G, and 14,337-14,378 TT deletion) were found. Interestingly, all of the nine patients in one family share the same mutation of Gly345Arg (14,034 G-->A) in the seventh exon. In another family, a single base mutation near the splice site (14,254 A-->G) was found in all of the three patients. In the last family, although a significant mutation was not found by direct sequencing, patients showed an abnormal 16 kb fragment in addition to the normal allele (21 kb Bcl I fragment). The C1INH mRNA expression of HAE patients in two families was not significantly different compared with that of normal controls.
Conclusion:
The two novel exonal mutations (G-->A and A-->G) and one large gene deletion were associated with the clinical phenotypes of HAE. Considering the normal C1INH mRNA levels but below normal protein levels in two families, their phenotypes would be associated with the post-translational defect.
