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

Autor(es)

Nicolicht, Priscila ^[1] ; Faria, Douglas O. S. ^[1] ; Martins-Silva, Leonardo ^[1] ; Maia, Luana S. M. ^[2] ; Moreno, Adriana S. ^[2] ; Karla Arruda, L. ^[2] ; Motta, Antonio A. ^[3] ; Grumach, Anete S. ^[4] ; Pesquero, Joao B. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Ctr Res & Mol Diag Genet Dis, Dept Biophys, Rua Pedro de Toledo 669, 9 Andar, BR-04039032 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Div Clin Immunol, Dept Med, Ribeirao Preto Med Sch, Ave Bandeirantes 3900, BR-14049900 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Div Clin Immunol & Allergy, Dept Med, USP Med Sch, Ave Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

^[4] Fac Med ABC, Div Clin Immunol, Ave Principe Gales 821, BR-09060650 Santo Andre, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Gene; v. 685, p. 179-185, FEB 15 2019.
• Citações Web of Science: 3

Resumo

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 AM 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 SERPINGI, otherwise not detected by Sanger sequencing, serving as a support technique for molecular diagnosis of HAE. (AU)

• Processo FAPESP: 14/27198-8 - Estabelecimento de um centro de pesquisa genética e molecular para desafios clínicos
• Beneficiário: João Bosco Pesquero
• Linha de fomento: Auxílio à Pesquisa - Temático