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Thromb Haemost 1997; 78(05): 1347-1351
DOI: 10.1055/s-0038-1665409
Review Article
Schattauer GmbH Stuttgart

Haemophilia B in Female Twins Caused by a Point Mutation in one Factor IX Gene and Nonrandom Inactivation Patterns of the X-Chromosomes

Winnie Schröder
1   The institute of Human Genetics, Ernst-Moritz-Arndt-University, Greifswald, Germany
,
Karin Wulff
1   The institute of Human Genetics, Ernst-Moritz-Arndt-University, Greifswald, Germany
,
Karin Wollina
2   Division of Haematology, Department of Paediatrics, Friedrich-Schiller-University, Jena and Klinikzentrum Bad Suiza, Germany
,
Falko H Herrmann
1   The institute of Human Genetics, Ernst-Moritz-Arndt-University, Greifswald, Germany
› Institutsangaben
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Publikationsverlauf

Received 26. 1997

Accepted after resubmission 09. Juli 1997

Publikationsdatum:
30. Juli 2018 (online)

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Summary

Haemophilia B is a X-linked recessive bleeding disorder with an incidence of 1:25,000-30,000 male birth. Usually female carriers are clinically normal. Phenotypic expression of the disease in female carriers is extremely rare.

We describe cytogenetically inconspicuous female identical twins both with factor IX levels below 2%, prolonged bleeding after venipuncture as well as haematomas after intramuscular injections. The father, suffering from a severe haemophilia B, is deceased. By sequencing one point mutation was characterized in heterozygote condition in the factor EX gene of the probands at nt 17678. This mutation leads to the substitution cystein 88 to tyrosine in the growth factor domain of the factor IX. Investigation of the X-chromosomal inactivation by comparison of methylation patterns of genomic DNA at locus DXS255 after digestion with Pst I and Pst I +Hha I and hybridisation with the probe M27β indicated a nonrandom pattern of X-chromosomal inactivation in the twins. In both girls, only the paternal X-chromosome was the active one leading to the phenotypic expression of haemophilia in the female carriers.

 

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