Hereditary Angioedema Clinical And Molecular Biology Research

Objective:Study the relationship of clinical characteristic, examination and follow-up in the patients with hereditary angioedema.Method:Collect the information of the patients with hereditary angioedema in PUMCH from 1985 to 2010. Discuss the clinical characteristic, examination and follow-up in 113 patients with hereditary angioedema by retrospective analysis.Results:1,There were 113 patients with hereditary angioedema,97 patients had definite type by examination in PUMCH, which were composed of 87patients with HAE-I,10 patients with HAE-II.2,C1INH was checked in 52 male(mean 0.081g/L) and 44 female (mean0.069g/L), which was higher in male (p=0.092).3,Sites of edema were positively correlated with course of disease (r=0.205, p=0.049) in 93 patients.4,The patients were divided into two groups by laryngeal edema. The patients with laryngeal edema had the characteristic of older, longer course, more sites of edema and lower function of C1INH.5,The patients were divided into two groups by abdominal pain. The sites of edema in abdominal pain group(2.7±0.9) were more than it in no abdominal pain group(1.7±0.8), (P=0.001).6,There were positive correlation between quantity and function of C1INH in 38 patients with HAE-I (r= 0.352, p= 0.030).7,Long-term prevention was used danazol in 24 patients, the dosage of male was more than it of female. The quantity and function of C1INH increased after treatment, from 0.08±0.06g/L to 0.12±0.07g/L (p= 0.05) and from 0.14±0.04U/ml to 0.26±0.05U/ml (p<0.001) respectively. C4 increased post-treatment obviously. The dosage of danazol had the high trend in male.Conclusion:Hereditary angioedema manifested as cutaneous and mucous edema, laryngeal edema was also the common manifestation of the disease, which had the relationship with the course and severity of the disease. The quantity and function of C1INH changed simultaneously. Danazol was the safe and effective treatment to the patients, and the maintenance dose of male had the high trend. C4 was the suitable index to monitor the disease. Objective:To identify the C1 inhibitor(C1-INH) gene mutation in Chinese HAE families, in order to study the molecular biology mechanism initially.Methods:A mutation specific polymerase chain reaction (PCR) was used to amplify the first to eighth exons of the C1-inhibitor gene, followed by gene sequencing. Sequencing results were compared with the normal sequences in GeneBank to locate the mutations.Results:There were four base pair deletions at position of exon3, exon7, and exon8 and eight point mutations at exon8 in twelve of HAE-Ⅰfamilies, three novel mutations were found among them, meanwhile three same point mutation in three of HAE-Ⅱfamilies, Codon CGC was converted to CAC, as a result, Arg at position 444 was replaced by His..Conclusion:We reported gene mutations in HAE-Ⅰfamilies and HAE-Ⅱfamilies simultaneously first in China. The type of gene mutation in HAE-Ⅰfamilies was heterogeneity, meanwhile the site of mutation located in different exons. A mutation of HAE-Ⅱfamilies all located in the reactive centre of the C1-INH gene. The group of deletion and nonsense mutation had a higher trend of laryngeal edema than the group of missense mutation.