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Normal C1 inhibitor mRNA expression level in type I hereditary angioedema patients: newly found C1 inhibitor gene mutations

Cited 13 time in Web of Science Cited 14 time in Scopus
Authors
Kang, H R; Yim, E Y; Oh, S Y; Chang, Y S; Kim, Y K; Cho, S H; Min, K U; Kim, Y Y
Issue Date
2006-01-18
Publisher
Wiley-Blackwell
Citation
Allergy. 2006 Feb;61(2):260-4.
Keywords
AdolescentAdultAgedAngioedema/*geneticsBlotting, SouthernChildComplement C1 Inactivator Proteins/*geneticsDNA Mutational AnalysisFemale*Genetic Predisposition to DiseaseHumansKoreaMaleMiddle AgedMutationPedigreeRNA, Messenger/*analysisReverse Transcriptase Polymerase Chain ReactionSerpins/*genetics
Abstract
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.
ISSN
0105-4538 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16409206

http://hdl.handle.net/10371/27570
DOI
https://doi.org/10.1111/j.1398-9995.2006.01010.x
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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