Genomics of bleeding disorders.
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.
Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust and Haemostasis Research Group, Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
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AC
Goodeve
A
A
Pavlova
J
J
Oldenburg
D000818:Animals; D001778:Blood Coagulation Disorders / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D001779:Blood Coagulation Factors / Q000009:adverse effects / Q000627:therapeutic use; D005820:Genetic Testing; D023281:Genomics; D006801:Humans; D007518:Isoantibodies / Q000235:genetics / Q000276:immunology; D011379:Prognosis
D001779:Blood Coagulation Factors; D007518:Isoantibodies
bleeding disorders; genetics; genomics; haemophilia; inhibitor development