Spectrum of clinical and genetic features of patients with inherited platelet disorder with suspected predisposition to hematological malignancies: a nationwide survey in Japan

Ann Oncol. 2016 May;27(5):887-95. doi: 10.1093/annonc/mdw066. Epub 2016 Feb 15.


Background: Inherited thrombocytopenia (IT) contains several forms of familial thrombocytopenia and some of them have propensity to hematological malignancies. The etiological and genetic features of this heterogeneous syndrome have not yet been elucidated.

Patients and methods: We conducted a nationwide survey to collect clinical information and samples from patients with familial thrombocytopenia and/or hematological malignancies in order to obtain a comprehensive understanding of IT.

Results: Among the 43 pedigrees with clinical samples, RUNX1 mutations were identified in 8 pedigrees (18.6%). While MYH9 and ANKRD26 mutations were identified in 2 and 1 pedigrees, respectively, no gene mutations were detected in the remaining 32 pedigrees from a panel of previously reported pathogenetic mutations. Clinical data were comparable between FPD/AML and non-FPD/AML probands.

Conclusions: Our study clarified that it is unexpectedly difficult to diagnose FPD/AML based on clinical information alone, and thus, genetic testing is strongly recommended. Our survey also identified some pedigrees with a strong family history of myelodysplastic syndromes of unknown origin. Additionally, there were 14 pedigrees in which three or more members were affected by immune thrombocytopenia (ITP), and a computer-aided simulation suggested that such a distribution almost never happens by coincidence, which implicates a genetic predisposition to ITP.

Keywords: FPD/AML; RUNX1; familial myelodysplastic syndrome; immune thrombocytopenia; inherited thrombocytopenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Coagulation Disorders, Inherited / epidemiology*
  • Blood Coagulation Disorders, Inherited / genetics
  • Blood Coagulation Disorders, Inherited / pathology
  • Blood Platelet Disorders / epidemiology*
  • Blood Platelet Disorders / genetics
  • Blood Platelet Disorders / pathology
  • Blood Platelets / pathology*
  • Child
  • Child, Preschool
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Hematologic Neoplasms / epidemiology*
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / pathology
  • Humans
  • Infant
  • Japan / epidemiology
  • Leukemia, Myeloid, Acute / epidemiology*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Mutation
  • Thrombocytopenia / epidemiology*
  • Thrombocytopenia / genetics
  • Thrombocytopenia / pathology


  • Core Binding Factor Alpha 2 Subunit
  • RUNX1 protein, human

Supplementary concepts

  • Platelet Disorder, Familial, with Associated Myeloid Malignancy