Gray platelet syndrome: Natural history of a large patient cohort and locus assignment to chromosome 3p

Gray platelet syndrome (GPS) is an inherited bleeding disorder characterized by macrothrombocytopenia and absence of platelet α-granules resulting in typical gray platelets on peripheral smears. GPS is associated with a bleeding tendency, myelofibrosis, and splenomegaly. Reports on GPS are limited to case presentations. The causative gene and underlying pathophysiology are largely unknown.We present the results of molecular genetic analysis of 116 individuals including 25 GPS patients from 14 independent families as well as novel clinical data on the natural history of the disease. The mode of inheritance was autosomal recessive (AR) in 11 and indeterminate in 3 families. Using genomewide linkage analysis, we mapped the AR-GPS gene to a 9.4-Mb interval on 3p21.1-3p22.1, containing 197 protein-coding genes. Sequencing of 1423 (69%) of the 2075 exons in the interval did not identify the GPS gene. Long-term follow-up data demonstrated the progressive nature of the thrombocytopenia and myelofibrosis of GPS resulting in fatal hemorrhages in some patients. We identified high serum vitamin B12 as a consistent, novel finding in GPS. Chromosome 3p21.1-3p22.1 has not been previously linked to a platelet disorder; identification of the GPS gene will likely lead to the discovery of novel components of platelet organelle biogenesis. This study is registered at www.clinicaltrials.gov as NCT00069680 and NCT00369421.

This research was originally published in Blood. Meral Gunay-Aygun et al. Gray platelet syndrome: natural history of a large patient cohort and locus assignment to chromosome 3p. Blood. 2010;116,23:. © the American Society of Hematology.

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Work Title Gray platelet syndrome: Natural history of a large patient cohort and locus assignment to chromosome 3p
Access
Open Access
Creators
  1. Meral Gunay-Aygun
  2. Yifat Zivony-Elboum
  3. Fatma Gumruk
  4. Dan Geiger
  5. Mualla Cetin
  6. Morad Khayat
  7. Robert Kleta
  8. Nehama Kfir
  9. Yair Anikster
  10. Judith Chezar
  11. Mauricio Arcos-Burgos
  12. Adel Shalata
  13. Horia Stanescu
  14. Joseph Manaster
  15. Mutlu Arat
  16. Hailey Edwards
  17. Andrew S. Freiberg
  18. P. Suzanne Hart
  19. Lauren C. Riney
  20. Katherine Patzel
  21. Pranoot Tanpaiboon
  22. Tom Markello
  23. Marjan Huizing
  24. Irina Maric
  25. McDonald Horne
  26. Beate E. Kehrel
  27. Kerstin Jurk
  28. Nancy F. Hansen
  29. Praveen F. Cherukuri
  30. Marypat Jones
  31. Pedro Cruz
  32. Jim C. Mullikin
  33. Alan Nurden
  34. James G. White
  35. William A. Gahl
  36. Tzippora Falik-Zaccai
Keyword
  1. Bleeding diathesis
  2. Blood platelets
  3. Chromosomes
  4. Follow-up
  5. Genes
  6. Genetic linkage analysis
  7. Genome
  8. Granules
  9. Gray platelet syndrome
  10. Hemorrhage
License In Copyright (Rights Reserved)
Work Type Article
Publisher
  1. Blood
Publication Date August 13, 2010
Publisher Identifier (DOI)
  1. https://doi.org/10.1182/blood-2010-05-286534
Deposited March 07, 2024

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Version 1
published

  • Created
  • Added gray_plt_1_2010-1.pdf
  • Added Creator Meral Gunay-Aygun
  • Added Creator Yifat Zivony-Elboum
  • Added Creator Fatma Gumruk
  • Added Creator Dan Geiger
  • Added Creator Mualla Cetin
  • Added Creator Morad Khayat
  • Added Creator Robert Kleta
  • Added Creator Nehama Kfir
  • Added Creator Yair Anikster
  • Added Creator Judith Chezar
  • Added Creator Mauricio Arcos-Burgos
  • Added Creator Adel Shalata
  • Added Creator Horia Stanescu
  • Added Creator Joseph Manaster
  • Added Creator Mutlu Arat
  • Added Creator Hailey Edwards
  • Added Creator Andrew S. Freiberg
  • Added Creator P. Suzanne Hart
  • Added Creator Lauren C. Riney
  • Added Creator Katherine Patzel
  • Added Creator Pranoot Tanpaiboon
  • Added Creator Tom Markello
  • Added Creator Marjan Huizing
  • Added Creator Irina Maric
  • Added Creator McDonald Horne
  • Added Creator Beate E. Kehrel
  • Added Creator Kerstin Jurk
  • Added Creator Nancy F. Hansen
  • Added Creator Praveen F. Cherukuri
  • Added Creator Marypat Jones
  • Added Creator Pedro Cruz
  • Added Creator Jim C. Mullikin
  • Added Creator Alan Nurden
  • Added Creator James G. White
  • Added Creator William A. Gahl
  • Added Creator Tzippora Falik-Zaccai
  • Published
  • Updated Keyword, Publication Date Show Changes
    Keyword
    • Bleeding diathesis, Blood platelets, Chromosomes, Follow-up, Genes, Genetic linkage analysis, Genome, Granules, Gray platelet syndrome, Hemorrhage
    Publication Date
    • 2010-12-02
    • 2010-08-13
  • Updated