Trisomy X conferring moderate hemophilia A by extremely skewed X-chromosome inactivation.
Res Pract Thromb Haemost
; 7(7): 102233, 2023 Oct.
Article
em En
| MEDLINE
| ID: mdl-38077808
ABSTRACT
Background:
Hemophilia carriers occasionally present with bleeding tendency due to skewed inactivation of normal F8 carrying X chromosome. Key Clinical Question Can extreme skewing of X-chromosome inactivation (XCI) with trisomy X cause low factor (F) VIII activity and bleeding in a hemophilia carrier?. ClinicalApproach:
A young female with low FVIII activity (2 IU/dL), who presented with history of frequent bleeding and F8 variant, NP_000123.1p.(Arg1800His), was identified. The mother was also confirmed genetically as hemophilia carrier. Karyotype was 47, XXX, multiplex ligation-dependent probe amplification for aneuploidy in the family identified trisomy X only in the index case. Digital polymerase chain reaction using leucocytes, urine, and oral mucosa identified one maternal F8 variant carrying and 2 wild-type F8 carrying X chromosomes, but it detected no somatic mosaicisms. Methylation-sensitive-HpaII-polymerase chain reaction assay showed predominantly activated maternal and 2 fully inactivated paternal X chromosomes. The XCI patterns using tissues of different developmental origins showed extremely skewed XCI.Conclusion:
Extreme skewing of XCI can occur even in hemophilia carriers with trisomy X, conferring frequent bleeding and low FVIII activity.
Texto completo:
1
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article