Pio Simone Ferreira, Oliveira Guilherme Corrêa de, Rezende Suely Meireles
Centro de Pesquisas Renè Rachou, FIOCRUZ.
Rev Assoc Med Bras (1992). 2009 Mar-Apr;55(2):213-9. doi: 10.1590/s0104-42302009000200029.
Hemophilias are bleeding disorders due to deficiency of the blood coagulation factor VIII (hemophilia A) or factor IX (hemophilia B), resulting from mutation on the gene coding for factor VIII or factor IX. Hemophilia A is more frequent than hemophilia B and affects 1:10,000 male newborns. The severity and frequency of hemorrhagic episodes is related to residual activity of factor VIII present in the plasma and relates to the type of mutation associated with the disorder. Cloning of the factor VIII gene has enabled researchers to better understand the molecular basis of hemophilia A, accounting to date, for more than 1,000 mutations associated with the disease. This comprehensive knowledge permits an improved comprehension of the genotype-phenotype relation, establishment of clinical policies when mutations related to higher risk of inhibitors development are known, identification of hemophilia carriers in case of women related to patients, implementation of a program of genetic counseling and discovery of structural-functional relationship between gene-protein. This article aims to review the molecular basis of hemophilia A, laboratory techniques used to characterize mutations and clinical implications involved in the molecular diagnosis of hemophilia A.
血友病是由于血液凝固因子VIII（甲型血友病）或因子IX（乙型血友病）缺乏而导致的出血性疾病，这是由编码因子VIII或因子IX的基因突变引起的。甲型血友病比乙型血友病更常见，每10000名男性新生儿中就有1人受影响。出血发作的严重程度和频率与血浆中存在的因子VIII的残余活性有关，并且与该疾病相关的突变类型有关。因子VIII基因的克隆使研究人员能够更好地理解甲型血友病的分子基础，迄今为止，已经发现了1000多种与该疾病相关的突变。这些全面的知识有助于更好地理解基因型与表型的关系，在已知与抑制剂产生高风险相关的突变时制定临床策略，在与患者相关的女性中识别血友病携带者，实施遗传咨询计划以及发现基因与蛋白质之间的结构-功能关系。本文旨在综述甲型血友病的分子基础、用于表征突变的实验室技术以及甲型血友病分子诊断中涉及的临床意义。
