title: Spectrum of clinical and genetic features of patients with inherited platelet disorder with suspected predisposition to hematological malignancies: a nationwide survey in Japan.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo.
authors.forename: A
authors.initials: A
authors.lastname: Yoshimi
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo.
authors.forename: T
authors.initials: T
authors.lastname: Toya
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo.
authors.forename: Y
authors.initials: Y
authors.lastname: Nannya
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Takaoka
authors.affiliation: Department of Hematology and Oncology, University of Yamanashi, Yamanashi.
authors.forename: K
authors.initials: K
authors.lastname: Kirito
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Hirosaki University, Aomori.
authors.forename: E
authors.initials: E
authors.lastname: Ito
authors.affiliation: Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo.
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: Department of Hematology/Oncology, Gunma Children's Medical Center, Gunma.
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: The Department of Hematology, Mitsui Memorial Hospital, Tokyo.
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi.
authors.forename: A
authors.initials: A
authors.lastname: Moriya-Saito
authors.affiliation: Department of Hematology, Japanese Red Cross Medical Center, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Hematology, Graduate School of Medicine, Juntendo University, Tokyo Department of Hematology and Oncology, Hiroshima University, Hiroshima.
authors.forename: H
authors.initials: H
authors.lastname: Harada
authors.affiliation: Department of Hematology, Graduate School of Medicine, Juntendo University, Tokyo.
authors.forename: N
authors.initials: N
authors.lastname: Komatsu
authors.affiliation: Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Usuki
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo.
authors.forename: M
authors.initials: M
authors.lastname: Ichikawa
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo kurokawa-tky@umin.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Kurokawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D025861:Blood Coagulation Disorders, Inherited / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D001791:Blood Platelet Disorders / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D001792:Blood Platelets / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D019337:Hematologic Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007223:Infant; D007564:Japan / Q000453:epidemiology; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013921:Thrombocytopenia / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human
keywords: FPD/AML; RUNX1; familial myelodysplastic syndrome; immune thrombocytopenia; inherited thrombocytopenia