Thromb Haemost 2007; 98(06): 1165-1169
DOI: 10.1160/TH07-02-0125
Rapid and Short Communication
Schattauer GmbH

A nonstop mutation in the factor (F)X gene of a severely haemorrhagic patient with complete absence of coagulation FX

Authors

  • Afshin Ameri*

    1   Department of Pediatrics, Division of Hematology and Oncology, Medical College of Georgia, Augusta, Georgia, USA
  • Deepa K. Machiah*

    2   Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
  • Thuy T. Tran*

    2   Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
  • Cynthia Channell

    2   Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
  • Valerie Crenshaw

    1   Department of Pediatrics, Division of Hematology and Oncology, Medical College of Georgia, Augusta, Georgia, USA
  • Karl Fernstrom

    2   Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
  • Manana Khachidze

    2   Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
  • Alexander Duncan

    2   Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
  • Sebastien Fuchs

    2   Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
  • Tom E. Howard

    2   Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
    4   Current address: Department of Pathology and Laboratory Medicine, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA
Further Information

Publication History

Received 29 April 2007

Accepted after revision 09 October 2007

Publication Date:
30 November 2017 (online)

Preview

Summary

We identified a previously unknown mutation by sequencing the factor (F)X gene in a severely haemorrhagic 14-year-old maleAfrican-American individual with undetectable plasma FX-activity and -antigen levels. This mutation, called F10-Augusta, was homozygote and is a combination of an 8bp insertion in flanking 3’-genomic-DNA and a 5bp terminal exon-8 deletion involving codons 437 and 438. Sequencing of RT-PCR and 3’-RACE products showed that the F10-Augusta transcript is normally processed but lacks an in-frame stop codon. An allele specific 3’-RACE-based RFLP assay demonstrated that the steady-state concentration of the mutant transcript was markedly lower than that of the wild-type message in total-RNA samples from the patient’s unaffected heterozygous parents. The recently discovered nonstop decay mechanism, a component pathway of the mRNA surveillance system, is a possible explanation for the reduced concentration of the mutant FX transcript. This is the first report implying such a mechanism in the pathogenesis of inherited bleeding disorders.

* These authors contributed equally to this work.