Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust and Haemostasis Research Group, Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
Haemophilia. 2014 May;20 Suppl 4(0 4):50-3. doi: 10.1111/hae.12424.
Molecular genetic tools are widely applied in inherited bleeding disorders. New genes involved in haemorrhagic disorders have been identified by genome wide linkage analysis on families with a specific phenotype. LMNA1 or MCFD in combined FV/FVIII-deficiency and VKORC1 in vitamin K coagulation factor deficiency type 2 are two examples. Identification of the causative gene mutation has become standard for most bleeding disorders. Knowledge of the causative mutation allows genetic counselling in affected families and most importantly adds to the pathophysiological understanding of phenotypes. Haemophilia A represents a model as the F8 gene mutation predicts the risk of developing an inhibitor and more recently also the bleeding phenotype. In this review novel genetic diagnostic strategies for bleeding disorders are outlined and inhibitor formation is presented as an example for clinical relevant phenotype/genotype correlation studies.
分子遗传学工具广泛应用于遗传性出血性疾病。通过对具有特定表型的家系进行全基因组连锁分析，已经发现了一些与出血性疾病相关的新基因。例如，联合 FV/FVIII 缺乏症中的 LMNA1 或 MCFD 以及维生素 K 凝血因子缺乏症 2 型中的 VKORC1。确定致病基因突变已成为大多数出血性疾病的标准。致病基因突变的知识可用于受影响家庭的遗传咨询，最重要的是，有助于增加对表型病理生理学的理解。血友病 A 是一个模型，因为 F8 基因突变可预测发生抑制剂的风险，最近还可预测出血表型。本综述概述了用于出血性疾病的新型遗传诊断策略，并以抑制剂形成作为临床相关表型/基因型相关性研究的一个例子。
