12th C1-inhibitor Deficiency & Angioedema Workshop , Budapest, Hungary, 3 June - 06 December 2021, pp.83
Background: In a small group (5-10%) of HAE-C1INH cases, a mutation could not be detected in the SERPING1 gene despite detailed investigations. As well as Type I and Type II HAE-C1INH, and HAE-nC1INH, several studies have reported the presence of HA1-C1INH cases with Type I HAE-C1INH phenotype but without a mutation. Despite no SERPING1 gene mutation in these patients diagnosed with type 1 HAE-C1INH, it is unknown why to have low C1INH function and low C1INH and C4 levels. However, it has been suggested that these patients may have a mutation preventing C1INH expression in the deep intronic region or untranslated region.
We previously performed a SERPING1 gene-targeted sequencing study to show the relationship between phenotypic diversity of HAE-C1INH and different mutations. As a result of the study performed with patients diagnosed with Type I HAE-C1INH, we reported having no SERPING1 gene mutation of five patients.
In this study, we aimed to determine possible variations in SERPING1 and other genes in these five patients by performing whole-exome sequencing (WES), which enables sequencing of all protein-coding regions in the whole genome.
Method: Genomic DNA samples, extracted from the peripheral blood samples of five patients, were used for WES. WES was performed on Illumina NextSeq 550 sequencing platform. Bioinformatic analysis of WES raw data was carried out with CLC Genomics 20.0.4. The variations, detected as a result of bioinformatics analysis, were also examined by scanning in VarSome and Franklin Genoox databases.
Results: The promoter of the SERPING1 gene was determined a variation (c.-22-2A>G) as heterozygosis in one of five patients. The variation has been indicated pathogenic in VarSome and likely pathogenic in Franklin Genoox.
Conclusions: This variation in the regulatory region was reported for the different populations such as Danish (by Bygum et al., 2011 and Veronez et al., 2019), French (by Ponard et al., 2020). Also, different variations, c.-22-2A>C and c.-22-2A>T, in the same region were reported by Aabom et al., 2017 and Ponard et al., 2020, respectively. With this study, we have shown that this variation exists in the Turkish population. Although this variation