Identification of an elusive

Background: Hereditary angioedema (HAE) is an autosomal dominant genetic disorder caused by mutations in the C1 esterase inhibitor gene, SERPING1, leading to overproduction of bradykinin and debilitating swelling attacks. Variants in the Methods: We consented and collected whole blood samples from three family members with clinical diagnoses of HAE. The samples underwent genomic DNA extraction and evaluation for purity prior to sequencing. The DNA samples were processed through a semi-automated whole exome library prep pipeline and sequenced. Results: Clinical variant analysis revealed two common benign variants of Summary: Without additional techniques following NGS and MLPA, such as a soft clipping analysis method, many difficult-to-detect large insertions and deletions may go undetected. We propose that a systematic approach to undetected HAE-causing mutation analysis, incorporating soft clipping as part of an overall strategy, would be more effective in identifying a small percentage of causal variants in approximately 5% of C1-esterase inhibitor HAE cases where no mutation is found by standard laboratory procedures, especially when there are high clinical suspicions of a familiar disorder.