Caracterização molecular da doença de von Willebrand tipo 2

• Ano de defesa: 2017
• Autor(a) principal: Samuel da Silva Freitas
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: coagulopatia; sequenciamento; diagnóstico; variantes genéticas; Doença de von Willebrand; Variação genética; Transtornos da coagulação sanguínea; Medicina; Doenças de von Willebrand
• Link de acesso: http://hdl.handle.net/1843/BUBD-AXNFP4

von Willebrand disease (VWD) is the most common inherited bleeding disorder, with a prevalence of symptomatic patients of 1:1,000 to 1:10,000. VWD is associated with genetic defects in the von Willebrand factor (vWF) gene, leading to quantitative (types 1 and 3) or qualitative deficiencies (type 2) of the factor. Diagnosis of subtypes 2A, 2B, 2M and 2N can be difficult as it requires the performance of specific coagulation tests, which are not broadly available in coagulation laboratories, particularly in developing countries. The aiming of this study was to identify variants associated with type 2 VWD by sequencing the exons 17, 18, 20 and 28 of the VWF gene in a cohort of patients clinically diagnosed as type 2 VWD. Exons 17, 18, 20 and 28 from VWF gene of 42 probands were sequenced. A total of 19 variants were identified in 34 probands. Most of the sequence variants were found in exon 28 (84.2%). Potentially pathogenic variants were identified in 18 probands (42.8%) with type 2 VWD. In conclusion, 10 potentially pathogenic variants and nine potentially benign variants were found in this cohort. In conclusion, eight potentially pathogenic variants in 13 probands associated with subtypes 2A, 2B and 2M and nine potentially pathogenic variants were encountered. A good response to DDAVP was observed in patients who presented four potentially pathogenic variants: Met740Ile, Arg1315Cys, Arg1374Cys and Arg1597Gln.