C1 esterase inhibitor (C1INH) plays a key role in the classical pathway of complement cascade. Since genetic mutations in C1INH have been reported to cause a decreased level of antigenic (type I) or functional (type II) C1INH, we sought to find unique mutations in C1 INH and evaluate the association between these mutations and type I HAE phenotypes in order to elucidate the mechanism of this disease.

Genomic DNA of C1INH from three unrelated families (12 HAE patients and 15 family members) was isolated. Amplification by PCR was done with primers comprising all eight exons and adjacent intron sequences and 805 bp preceding the transcription start site. PCR products were directly sequenced.

We found 8 previously unreported mutations in C1INH gene (2311 T→C, 14034 G→A, 16830 G→A, and 16979-16980 G insertion in exons; 738 G→A, 8531 A→G, 14254A→G, and 14337-14378 TT deletion in introns). Gly345Arg (14034 G→A) in the seventh exon of C1INH was found in all seven patients while 12 healthy members of the same family did not show this mutation. 14254 A→G, a single base change near the splice site, was also found in three patients of another family. In the third family including two HAE patients, there was no mutation constantly related with their phenotypes.

We report three families whose members presented as recurrent angioedema. We found two SNPs in C1 INH gene which were correlated with HAE phenotype.