Elsevier

The Lancet

Volume 340, Issue 8827, 31 October 1992, Pages 1066-1067
The Lancet

SHORT REPORTS
Factor VIII gene explains all cases of haemophilia A

https://doi.org/10.1016/0140-6736(92)93080-7Get rights and content

Abstract

Using an mRNA-based method to examine haemophilia A mutations we provide an explanation for the puzzling report that half of the mutations causing severe disease are not detected by analysis of the putative promoter, exons, and most exon/intron boundaries of the factor VIII gene. An unusual cluster of mutations involving regions of intron 22 not examined earlier leads to defective joining of exons 22 and 23 in the mRNA and caused haemophilia A in 10/24 severely affected UK patients.

References (8)

There are more references available in the full text version of this article.

Cited by (66)

  • Disorders of Hemostasis and Thrombosis

    2022, Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics: Hematologic, Renal, and Immunologic Disorders
  • Hunting down factor VIII in the immunopeptidome

    2016, Cellular Immunology
    Citation Excerpt :

    Based on this it was proposed that severe hemophilia A patients with the intron 22 inversion should be considered as intracellular-CRM positive and not CRM negative [13]. These results are in accordance with early studies by Naylor and co-workers who have provided evidence for the presence of F8 gene transcripts in PBMC of healthy individuals and patient with an intron 22 inversion [14]. The authors claim that the entire primary amino acid sequence of FVIII is represented in the predicted protein products of hemophilia A patients with the intron 22 inversion.

  • Molecular Diagnostics for Coagulopathies

    2016, Diagnostic Molecular Pathology: A Guide to Applied Molecular Testing
  • Hemophilias and Other Disorders of Hemostasis

    2013, Emery and Rimoin's Principles and Practice of Medical Genetics
  • Lack of F8 mRNA: A novel mechanism leading to hemophilia A

    2006, Blood
    Citation Excerpt :

    Therefore, this absence of detectable expression in this patient could be because the studied mRNA are isolated from total blood that expresses only low levels of F8. Two reasons argue against this: (1) in humans an ectopic expression of F8 in total blood can be detected, and this is widely used to screen for mutations or rearrangements in the F8 cDNA13-15; (2) the results obtained in control subjects and the reproducibility and consistency of the experiments in the patient, his mother, and his sister should exclude any bias being specific for ectopic lymphocyte RT-PCR. The absence of detectable expression of the GA allele in the lymphocyte-derived RNA in both the mother and the sister could theoretically also be the result of skewed X-chromosome inactivation that is leaving only the allele from the active X chromosome to be actively expressed.

View all citing articles on Scopus
View full text