Mutational spectrum and geno-phenotype correlation in Chinese families with hereditary angioedema

Background: Hereditary angioedema is a rare autosomal dominant disease, and its correlation between genotype and phenotype seems not to exist. So far, there are very few studies on Chinese population. We aimed to establish a Chinese genetic database of hereditary angioedema and investigated the potential correlation between genotype and phenotype.

Method: All the eight exons and intron-exon boundaries of C1 inhibitor gene were detected in 48 unrelated families with HAE. The correlations between genotype and clinical parameters were evaluated by R statistical software.

Results: Thirty-five different mutations (25 of them were novel) and 7 SNPs (3 of them were novel) were identified. Significant difference was found in the level of C1 inhibitor antigen (P = 0.01793) between different groups of mutational types. The correlation between different groups of mutational types and the level of C1 inhibitor antigen (0.5047, P = 0.00027) was significant. The different groups of mutational types showed neither difference nor correlations of clinical parameters (severity score and the level of C1 inhibitor function).

Conclusion: It appears that nonsense, frameshift, and mutations on Arg466 can cause lower level of C1 inhibitor antigen than missense and in-frame mutations; however, it does not affect severity of symptoms.