Lethagen, Stefan Rune3; Dunø, Morten2; Nielsen, Lars Bo1
1 Klinisk Biokemisk Afdeling, Diagnostisk Center, Rigshospitalet, The Capital Region of Denmark2 Klinisk Genetisk Klinik, Juliane Marie Centre, Rigshospitalet, The Capital Region of Denmark3 Institut for Klinisk Medicin
Hemophilia is an inherited bleeding disorder primarily caused by deficiency of coagulation factor (F)VIII (hemophilia A) or FIX (hemophilia B). Both conditions are X-linked. More than 2100 different F8 mutations have been described, the most common being a 500 kb inversion involving exon 1 to exon 22. In hemophilia B, more than 1100 unique F9 mutations have been described scattered all over the gene. Carrier analysis, genetic counseling, prenatal and pre-implantation genetic diagnosis are all based on correct identifying the disease-causing mutation. Linkage analysis can be considered when the causative mutation is unknown. More rare bleeding disorders are generally recessively inherited, and are often caused by mutations that are specific for individual families, and mutations are scattered throughout the genes. Laboratories performing molecular genetic analyses must have validated internal quality control systems in place, and participate in established external quality assessment programs.
Application of Molecular Genetics To the Investigation of Inherited Bleeding Disorders, 2013, p. 115-123