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Molecular Analysis of the ERGIC-53 Gene in 35 Families With Combined Factor V-Factor VIII Deficiency
Journal article

Molecular Analysis of the ERGIC-53 Gene in 35 Families With Combined Factor V-Factor VIII Deficiency

  • Neerman-Arbez, M. 1 From the Department of Genetics and Microbiology, Division of Medical Genetics, University of Geneva Medical School; Haemostasis Research Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK; the Division of Medical Genetics, Cantonal Hospital of Geneva, Switzerland; Bonomi Haemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy; and the Department of Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI.
  • Johnson, K.M. 1 From the Department of Genetics and Microbiology, Division of Medical Genetics, University of Geneva Medical School; Haemostasis Research Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK; the Division of Medical Genetics, Cantonal Hospital of Geneva, Switzerland; Bonomi Haemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy; and the Department of Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI.
  • Morris, M.A. 1 From the Department of Genetics and Microbiology, Division of Medical Genetics, University of Geneva Medical School; Haemostasis Research Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK; the Division of Medical Genetics, Cantonal Hospital of Geneva, Switzerland; Bonomi Haemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy; and the Department of Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI.
  • McVey, J.H. 1 From the Department of Genetics and Microbiology, Division of Medical Genetics, University of Geneva Medical School; Haemostasis Research Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK; the Division of Medical Genetics, Cantonal Hospital of Geneva, Switzerland; Bonomi Haemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy; and the Department of Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI.
  • Peyvandi, F. 1 From the Department of Genetics and Microbiology, Division of Medical Genetics, University of Geneva Medical School; Haemostasis Research Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK; the Division of Medical Genetics, Cantonal Hospital of Geneva, Switzerland; Bonomi Haemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy; and the Department of Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI.
  • Nichols, W.C. 1 From the Department of Genetics and Microbiology, Division of Medical Genetics, University of Geneva Medical School; Haemostasis Research Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK; the Division of Medical Genetics, Cantonal Hospital of Geneva, Switzerland; Bonomi Haemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy; and the Department of Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI.
  • Ginsburg, D. 1 From the Department of Genetics and Microbiology, Division of Medical Genetics, University of Geneva Medical School; Haemostasis Research Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK; the Division of Medical Genetics, Cantonal Hospital of Geneva, Switzerland; Bonomi Haemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy; and the Department of Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI.
  • Rossier, C. 1 From the Department of Genetics and Microbiology, Division of Medical Genetics, University of Geneva Medical School; Haemostasis Research Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK; the Division of Medical Genetics, Cantonal Hospital of Geneva, Switzerland; Bonomi Haemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy; and the Department of Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI.
  • Antonarakis, S.E. 1 From the Department of Genetics and Microbiology, Division of Medical Genetics, University of Geneva Medical School; Haemostasis Research Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK; the Division of Medical Genetics, Cantonal Hospital of Geneva, Switzerland; Bonomi Haemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy; and the Department of Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI.
  • Tuddenham, E.G.D. 1 From the Department of Genetics and Microbiology, Division of Medical Genetics, University of Geneva Medical School; Haemostasis Research Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK; the Division of Medical Genetics, Cantonal Hospital of Geneva, Switzerland; Bonomi Haemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy; and the Department of Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI.
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Published in:
  • Blood. - American Society of Hematology. - 1999, vol. 93, no. 7, p. 2253-2260
Immunology
Cell Biology
Biochemistry
Hematology
English Abstract
Combined factor V-factor VIII deficiency (F5F8D) is a rare, autosomal recessive coagulation disorder in which the levels of both coagulation factors V and VIII are diminished. The F5F8D locus was previously mapped to a 1-cM interval on chromosome 18q21. Mutations in a candidate gene in this region, ERGIC-53, were recently found to be associated with the coagulation defect in nine Jewish families. We performed single-strand conformation and sequence analysis of the ERGIC-53 gene in 35 F5F8D families of different ethnic origins. We identified 13 distinct mutations accounting for 52 of 70 mutant alleles. These were 3 splice site mutations, 6 insertions and deletions resulting in translational frameshifts, 3 nonsense codons, and elimination of the translation initiation codon. These mutations are predicted to result in synthesis of either a truncated protein product or no protein at all. This study revealed that F5F8D shows extensive allelic heterogeneity and all ERGIC-53 mutations resulting in F5F8D are “null.” Approximately 26% of the mutations have not been identified, suggesting that lesions in regulatory elements or severe abnormalities within the introns may be responsible for the disease in these individuals. In two such families, ERGIC-53 protein was detectable at normal levels in patients’ lymphocytes, raising the further possibility of defects at other genetic loci.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/287688
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