Identification of an elusive deletion in a family with hereditary angioedema type I utilizing soft clipping.

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 gene are typically detected in a clinical setting by DNA sequencing or multiplex ligation-dependent probe amplification (MLPA), with over 893 total variants identified. Approximately 5% of patients with C1-esterase inhibitor deficiencies do not have detectable pathogenic variants.

Fragment-oriented synthesis: β-elaboration of cyclic amine fragments using enecarbamates as platform intermediates.

A strategy for the β-sp3 functionalisation of cyclic amines is described. Regioselective conversion of protected amines to enecarbamates is achieved through electrochemical oxidation; these intermediates can be derivatised by functionalised alkyl halides under photoredox catalysis. The potential of the methods is highlighted by direct growth of a DCP2B-binding fragment.