Dataset Information

Trisomy X conferring moderate hemophilia A by extremely skewed X-chromosome inactivation.

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?.

Clinical approach

A young female with low FVIII activity (2 IU/dL), who presented with history of frequent bleeding and F8 variant, NP_000123.1:p.(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.

SUBMITTER: Shinozawa K

PROVIDER: S-EPMC10704502 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Trisomy X conferring moderate hemophilia A by extremely skewed X-chromosome inactivation.

Shinozawa Keiko K Niiya Kenji K Fujimoto Seiichi S Bingo Masato M Fukutake Katsuyuki K Kinai Ei E

Research and practice in thrombosis and haemostasis 20231017 7

<h4>Background</h4>Hemophilia carriers occasionally present with bleeding tendency due to skewed inactivation of normal <i>F8</i> carrying X chromosome.<h4>Key clinical question</h4>Can extreme skewing of X-chromosome inactivation (XCI) with trisomy X cause low factor (F) VIII activity and bleeding in a hemophilia carrier?.<h4>Clinical approach</h4>A young female with low FVIII activity (2 IU/dL), who presented with history of frequent bleeding and <i>F8</i> variant, NP_000123.1:p.(Arg1800His), ...[more]

PMID: 38077808

Similar Datasets

Project description:BackgroundX chromosome inactivation (XCI) is the mechanism by which the X-linked gene dosage is adjusted between the sexes. Evidence shows that many sex-specific diseases have their basis in X chromosome biology. While female schizophrenia patients often have a delayed age of disease onset and clinical phenotypes that are different from those of males, it is unknown whether the sex differences in schizophrenia are associated with X-linked gene dosage and the choice of X chromosome silencing in female cells. Previous studies demonstrated that sex chromosome aneuploidies may be related to the pathogeneses of some psychiatric diseases. Here, we examined the changes in skewed XCI in patients with schizophrenia.MethodsA total of 109 female schizophrenia (SCZ) patients and 80 age- and sex-matched healthy controls (CNTLs) were included in this study. We evaluated clinical features including disease onset age, disease duration, clinical symptoms by the Positive and Negative Syndrome Scale (PANSS) and antipsychotic treatment dosages. The XCI skewing patterns were analyzed by the methylation profile of the HUMARA gene found in DNA isolated from SCZ patient and CNTL leukocytes in the three age groups.ResultsFirst, we found that the frequency of skewed XCI in SCZ patients was 4 times more than that in the age- and sex-matched CNTLs (p < 0.01). Second, we found an earlier onset of severe XCI skewing in the SCZ patients than in CNTLs. Third, we demonstrated a close relationship between the severity of skewed XCI and schizophrenic symptoms (PANSS score ≥ 90) as well as the age of disease onset. Fourth, we demonstrated that the skewed XCI in SCZ patients was not transmitted from the patients' mothers.LimitationsThe XCI skewing pattern might differ depending on tissues or organs. Although this is the first study to explore skewed XCI in SCZ, in the future, samples from different tissues or cells in SCZ patients might be important for understanding the impact of skewed XCI in this disease.ConclusionOur study, for the first time, investigated skewed XCI in female SCZ patients and presented a potential mechanism for the sex differences in SCZ. Our data also suggested that XCI might be a potential target for the development of female-specific interventions for SCZ.

Dataset Information

Trisomy X conferring moderate hemophilia A by extremely skewed X-chromosome inactivation.

Background

Key clinical question

Clinical approach

Conclusion

Publications

Trisomy X conferring moderate hemophilia A by extremely skewed X-chromosome inactivation.

Similar Datasets

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