Endocrine Abstracts

Background

The reported HMBS mutations of acute intermittent porphyria(AIP) have been increasing gradually in China. We aim to explore its mutation characteristic in China and improve the understanding of its molecular heterogeneity.

Material/methods

We searched the literature about Chinese AIP patients with HMBS mutation in the PubMed, CNKI, Wanfang and CQVIP database, and 3 AIP patients with HMBS mutation in our hospital were included. We analyzed the characteristic of these mutations in mutation site, type and frequency. The pathogenicity of all exon mutations were predicted by Mutation Taster.

Results

Totally, 66 unrelated AIP families were enrolled in this study, and 50 mutations were detected, including 17 missense mutations, 15 frameshift mutations, 11 splicing mutations, 6 nonsense mutations and 1 codon mutation. Exon mutations were mainly concentrated in exon 11 and 14(50%). Most of the mutations had the family specificity, but there were 8 mutations occurred in multiple families. P.R173W was the most common mutation, which occurred in 8 unrelated families. The predicted effects of c. 913C>A 1071delT and c.1078_1132del were polymorphisms, but the others were pathogenicity. C.160delA could not be predicted by Mutation Taster because it was located in the junction of exons and introns.

Conclusion

This is the first comprehensive analysis of HMBS mutation in China. Genetic analysis revealed that missense mutation accounted for the largest proportion and the p.R173W was the most common mutation. In addition, the pathogenicity prediction of bioinformatics software can only provide reference value, so further functional verification test is necessary.