INCREASED AGE RELATED EXPRESSION OF FVIII IN TWO UNRELATED FEMALES WITH SEVERE HEMOPHILIA A AND NONRANDOM X-INACTIVATION
Abstract number: P-M-119
Gruppo1 R.A., Davies1 S., Balasa1 V.V.
1Division of Hematology Oncology, Cincinnati Children's Hospital Medical Center and The University of Cincinnati College of Medicine, Cincinnati, United States
How-to-cite Gruppo RA, Davies S, Balasa VV. INCREASED AGE RELATED EXPRESSION OF FVIII IN TWO UNRELATED FEMALES WITH SEVERE HEMOPHILIA A AND NONRANDOM X-INACTIVATION. J Thromb Haemost 2007; 5 Supplement 2: P-M-119
Introduction: Several cases of females with severe hemophilia A due to skewed X-inactivation have been reported. In these individuals improvement in FVIII levels with age has never been reported. We report 2 unrelated females who presented with severe hemophilia A (FVIII < 1%) early in life whose FVIII levels increased to > 5% during childhood.
Methods: CASE 1: 21 yo female diagnosed with severe hemophilia A (FVIII<1%) at 19 mos. Brother and maternal uncle had severe Hemophilia A. Patient lost to follow-up until age 19 yrs when repeat FVIII was 6-9%. CASE 2: 14 yo female diagnosed with severe Hemophilia A (FVIII<1%) at age 5 mos. Family history is negative for hemophilia. Between 6 to 14 yrs FVIII gradually increased to 7%. In both cases spontaneous soft tissue and joint hemorrhages were observed in early life with a change to mild phenotype with age.
FVIII gene mutation analysis was performed by the Clin. Mol. Diag. Lab, City of Hope, Duarte, CA from genomic DNA covering 8.8 kb of the FVIII gene. X chromosome inactivation studies were performed by SD after digestion of DNA with HpaII and subjected to PCR amplification of polymorphic CAG-repeat sequence in exon 1 of the human androgen receptor gene (HUMARA).
Results: In CASE 1 no FVIII gene mutation was identified. CASE 2 was heterozygous for type 2 FVIII gene inversion. Chromosome analysis was normal. Clonal X-inactivation analysis showed an extremely skewed profile (100:0)in both cases.
Conclusions: These unrelated cases are the first reported examples of a gradual age-related increase in the expression of FVIII in females with severe Hemophilia A associated with nonrandom X-inactivation. The mechanism for increased factor VIII expression with age remains to be elucidated.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
||XXIst ISTH Congress
| Back to top