Study of VTN, PLG and other coagulation genes in atypical Hemolytic Uremic Syndrome (aHUS)

• Autor(a) principal: Malva, Jéssica Filipa Pires
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/30449
• topic: Atypical hemolytic uremic syndrome; Thrombotic microangiopathies; Genotype; VTN; PLG; Other coagulation genes; Molecular diagnostic techniques; Phenotype

Background: Atypical hemolytic uremic syndrome is a rare variant of thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia and, occasionally, acute renal failure. This condition is often idiopathic and may also be secondary to other pathologies or due to genetic causes - variants in the complement genes (C3, CFB, CFH, CFI, MCP, THBD). These changes, in most cases, lead to hyperactivation of the pathway complement and consequently result in the formation of microvascular thrombi that affect, mainly, the renal function. However, other possible genetic causes of this pathology have emerged recently, in genes not related to complement, VTN, PLG, among other coagulation genes. Objectives and Methods: In order to deepen the genotype/phenotype correlation in patients with aHUS, we analyzed 45 genes in 50 patients using Sanger sequencing for the VTN gene and a custom next generation sequencing gene panel (NGS) for PLG and other coagulation genes. Results: In total, 53 different rare variants were identified in VTN, PLG, ADAMTS13, ANKRD26, F5, F7, F8, F10, F13A1, FGA, FGB, FGG, GP6, ITGA2B, ITGB3, NBEAL2, PLAT, PROC, PROS1, SERPINC1, SERPINE1, SERPINF2, TUBB1 and VWF. Of which we identified 8 pathogenic variants, 11 probably pathogenic, 14 uncertain significance and 20 probably benign. Conclusions: This study did not imply VTN and PLG in particular as important contributors to aHUS. However, we found variants in several genes that could be a genetic background in these patients, and to have a cumulative effect on both systems - coagulation and complement.