Mutation update of SERPING1 related to hereditary angioedema in the Chinese population

BACKGROUND: Hereditary angioedema (HAE) is a rare disease characterized by recurrent attacks of severe swellings of the skin and submucosa. More than 900 variants of the SERPING1 gene associated with HAE have been identified. However, only approximately 50 variants have been identified in the Chinese population. This study aimed to update the mutational spectrum in Chinese HAE patients and provide evidence for the accurate diagnosis of HAE. METHODS: A total of 97 unrelated HAE patients were enrolled in the study. Sanger sequencing and multiple ligation-dependent probe amplification analysis were used to identify the variants in the SERPING1 gene. The variants were reviewed in a number of databases, including the Human Gene Mutation Database (HGMD) (http://www.hgmd.cf.ac.uk/) and the Leiden Open Variation Database (LOVD, https://databases.lovd.nl/shared/variants/SERPING1). The American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) criteria was used to determine the pathogenicity of the variants. RESULTS: Of the 97 patients, 76 different variants were identified in 90 of them and no disease-causing variants were identified in the remaining 7 patients. Among the 76 variants, 35 variants were novel and submitted to ClinVar. Missense and in-frame variants were the most common variants (36.8%), followed by frameshift (28.9%), nonsense (14.5%), splice site (13.2%) variants, and gross deletions/duplications (6.6%). CONCLUSIONS: Our findings broaden the mutational spectrum of SERPING1 and provide evidence for accurate diagnosis and predictive genetic counseling. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41065-022-00242-z.