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Hamostaseologie 2010; 30(S 01): S150-S152
DOI: 10.1055/s-0037-1619099
Original article
Schattauer GmbH

Molecular analysis of FVIII gene in severe HA patients of Costa Rica

Prevalence of intron 1 and 22 inversion
L. Salazar-Sánchez
1   Centre for Research in Haematology and related disorders (CIHATA), University of Costa Rica
,
G. Jiménez-Cruz
2   Haematology Department, México Hospital, San José, Costa Rica
,
M. Mendez
1   Centre for Research in Haematology and related disorders (CIHATA), University of Costa Rica
,
P. Chaverri
2   Haematology Department, México Hospital, San José, Costa Rica
,
P. Alvarado
1   Centre for Research in Haematology and related disorders (CIHATA), University of Costa Rica
,
W. Schröder
3   Institute of Human Genetics, University Greifswald, Germany
,
K. Wulff
3   Institute of Human Genetics, University Greifswald, Germany
,
M. Sandoval
2   Haematology Department, México Hospital, San José, Costa Rica
,
F. H. Herrmann
3   Institute of Human Genetics, University Greifswald, Germany
,
A. Pavlova
4   Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Germany
,
J. Oldenburg
4   Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
23 December 2017 (online)

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Summary

Haemophilia A (HA) is X-chromosome linked bleeding disorders caused by deficiency of the coagulation factor VIII (FVIII). It is caused by FVIII gene intron 22 inversion (Inv22) in approximately 45% and by intron 1 inversion (Inv1) in 5% of the patients. Both inversions occur as a result of intrachromosomal recombination between homologous regions, in intron 1 or 22 and their extragenic copy located telomeric to the FVIII gene. The aim of this study was to analyze the presence of these mutations in 25 HA Costa Rican families. Patients, methods: We studied 34 HA patients and 110 unrelated obligate members and possible carriers for the presence of Inv22or Inv1. Standard analyses of the factor VIII gene were used incl. Southern blot and long-range polymerase chain reaction for inversion analysis. Results: We found altered Inv22 restriction profiles in 21 patients and 37 carriers. It was found type 1 and type 2 of the inversion of Inv22. During the screening for Inv1 among the HA patient, who were Inv22 negative, we did not found this mutation. Discussion: Our data highlight the importance of the analysis of Inv22 for their association with development of inhibitors in the HA patients and we are continuous searching of Inv1 mutation. This knowledge represents a step for genetic counseling and prevention of the inhibitor development.

Keywords

Haemophilia A - intron 1 - intron 22 - Costa Rica - carriers
 

  • References

  • 1 Bagnall RD, Waseem N, Green PM, Giannelli F. Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe Hemophilia A. Blood 2002; 99: 168-174.
    CrossrefPubMedSearch in Google Scholar
  • 2 Brinke A, Naylor J, Green PM. et al. Two chimeric transcription units results from an inversion breaking intron 1 of the factor VIII gene and region reportedly affected by reciprocal translocation in T-cell leukemia. H Molec 1996; 05: 1945-1951.
    PubMedSearch in Google Scholar
  • 3 El-Maarri O, Oldenburg J, Handec AG. Intron 22-specific long PCR for the Xba I polymorphism in the factor VIII gene. Br J Haematol 1999; 105: 1120-1122.
    CrossrefPubMedSearch in Google Scholar
  • 4 Gitschier J, Wood WI, Goralka TM. et al. Characterization of the human factor VIII gene. Nature 1984; 312: 326-330.
    CrossrefPubMedSearch in Google Scholar
  • 5 Herrmann FH, Wehnert M, Schröder W, Wulff K. Genomic diagnosis of haemophilia A and B. Thromb Haemorrh Disorders 1990; 02: 11-15.
    PubMedSearch in Google Scholar
  • 6 Lakich D, Kazazian H, Antonarakis SE, Gitschier J. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nature Genetics 1993; 05: 236-241.
    CrossrefPubMedSearch in Google Scholar
  • 7 Naylor JA, Buck D, Green PM. et al. Investigation of the Factor VIII intron 22 repeated region (int22h) and the associated inversion junctions. Hum Mol Genet 1995; 04: 1217-1224.
    CrossrefPubMedSearch in Google Scholar
  • 8 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
    CrossrefPubMedSearch in Google Scholar
  • 9 Naylor JA, Buck D, Green PM. et al. Investigation of the factor VIII intron 22 repeated region (intzzh) and the associated inversion junctions. Human Mol Genet 1995; 04: 1217-1224.
    CrossrefPubMedSearch in Google Scholar