Gene mapping strategy for Alu elements rearrangements: detection of new large deletions in the SERPING1 gene causing hereditary angioedema in Brazilian families

Background Hereditary angioedema (HAE) is a rare genetic disorder mainly caused by mutations in the SERPING1 gene, determining a deficit of C1 inhibitor (C1-INH). In approximately 10% of the cases, HAE with C1-INH deficiency (C1-INH-HAE) is caused by large gene rearrangements, which are not detected by Sanger sequencing. Here we present the exon quantification technique (EQT), a molecular diagnostic test for the detection of large genetic rearrangements in SERPING1, mapping the exact size and location of the deletion caused by the recombination of Alu elements. EQT analysis was performed on total DNA extracted from blood of patients belonging to two Brazilian families with a medical history of HAE, low plasma levels of C4 and C1-INH and no pathogenic alteration in SERPING1 analyzed by Sanger sequencing. Results Two large deletions were found, one of 1356 pb and one of 1804 pb, which resulted from recombination of two Alu elements present in introns 3 and 4 of the gene. Conclusion These results showed that the EQT could be used as a simple, rapid, and efficient diagnosis test for analysis of large deletions and insertions involving SERPING1, otherwise not detected by Sanger sequencing, serving as a support technique for molecular diagnosis of HAE.