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Session


Keywords: Diagnostics; Genetic testing; Mutation detection; X-inactivation; X-linked disease

Authors:
G.C. Ma 1; S.P. Chang 1; M.C. Shen 2,3; M. Chen 1,4,5,6

Affiliations:
1) Department of Genomic Medicine, Changhua Christian Hospital, Changhua, Taiwan; 2) Division of Hematology-Oncology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan; 3) Hemophilia Treatment and Thrombosis Center, Changhua Christian Hospital, Changhua 50006, Taiwan; 4) Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua 50006, Taiwan; 5) Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 10041, Taiwan; 6) Department of Medical Genetics, National Taiwan University Hospital, Taipei 10041, Taiwan


Hemophilia A (HA) and B (HB) are X-linked recessive bleeding disorders caused by defects in the factor VIII and factor IX. Patients of HA and HB are typically hemizygous males and females homozygous or compound heterozygous for mutant F8 or F9. Symptomatic female carriers are relatively rare. Here, we report three families afflicted with female hemophilia, one with severe HA, another with moderate HA and the other with severe HB. Cytogenetics, molecular analyses on F8 and F9, and X-skewed inactivation assay were performed to determine the genetic defects of diseases. All the three female patients are demonstrated to carry a heterozygous mutation for the F8 or F9 (one mutation is inherited and the remaining two mutations are sporadic). In one HA and one HB patients, highly shewed inactivation of the wild-type X-chromosome (100%) was noted, which are thought to be responsible for the HA and HB. Our result highlight the importance of X-chromosome inactivation analysis to explore the underlying cause of affected females with X-linked recessive diseases (e.g. HA and HB) when only one mutant allele was determined.