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Supplementary Material
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The pedigrees (PGs) 1, 2, 3, 4, 12, 13, 15 have been already described. 1-4
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The characteristics of each new PG and the significance of RUNX1 mutation are described below.
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Familial trees are presented in Supplementary Figure 1A, the number of patients and PGs are presented
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in Table 1.
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* PG5, mutation p.P218S: Two identical twins (patients 10,11) have been diagnosed FPD/AML when
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they were 5 years old with a thrombocytopenia at 30-40 G/l, the other members of the family couldn’t be
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studied (refusal).
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* PG6, mutation p.G108V: The proband (III-1, patient 12) developed a T-ALL at the age of 14 years old.
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His uncle and his grand-father had thrombocytopenia. The G108V mutation is predicted as deleterious
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according to prediction software. 5
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* PG7, mutation p.D305TfsX262: The proband (II-4, patient 13) developed AML at 37 years. She had a
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medical history of thrombocytopenia with metrorrhagia. Her daughter and her mother have both
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thrombocytopenia, her three sisters have a normal platelet count. The frameshift RUNX1 mutation occurs
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in the transactivation domain.
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* PG8, mutation p.H377PfsX191: The patient (patient 14) had thrombocytopenia discovered at the age of
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3 years, the other members of the family couldn’t be studied (refusal). She developed AML when she was
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12 years old and died from infectious complications. The frameshift RUNX1 mutation occurs in the
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transactivation domain.
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* PG9, mutation p.G108V: The proband (II-1, patient 15) is thrombocytopenic. Her father died from
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AML and her sister is thrombocytopenic too. The mutation G108V is predicted as deleterious according
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to prediction software. 5
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* PG10, mutation p.G143RfsX43: The proband (I-1, patient 16) developed AML at 36 years. His
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daughter and his son are both thrombocytopenic with the same RUNX1 mutation. He underwent an
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allograft from his HLA-identical brother, who is not thrombocytopenic and not mutated for RUNX1. The
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frameshift mutation is in the DNA binding domain of RUNX1.
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* PG11, mutation p.T169R: The proband (I-1, patient 17), his two daughters (II-2,3, patients 18,19) and
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his son (II-1, patient 20) are all thrombocytopenic and mutated for RUNX1, with bleeding history. This
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mutation is predicted as deleterious according to prediction software. 5
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* PG14, mutation p.T121HfsX9: The proband (I-2, patient 23) has thrombocytopenia. His son (II-1,
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patient 24) has thrombocytopenia with bleeding history. He developed AML at the age of 6. They are
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both mutated for RUNX1, with a frameshift mutation occurring in the DNA binding domain.
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References
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1.
Preudhomme C, Renneville A, Bourdon V, Philippe N, Roche-Lestienne C, Boissel N, et al. High
frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet
disorder. Blood 2009 May 28; 113(22): 5583-5587.
2.
Beri-Dexheimer M, Latger-Cannard V, Philippe C, Bonnet C, Chambon P, Roth V, et al. Clinical
phenotype of germline RUNX1 haploinsufficiency: from point mutations to large genomic
deletions. European journal of human genetics : EJHG 2008 Aug; 16(8): 1014-1018.
3.
Bluteau D, Gilles L, Hilpert M, Antony-Debre I, James C, Debili N, et al. Down-regulation of the
RUNX1-target gene NR4A3 contributes to hematopoiesis deregulation in familial platelet
disorder/acute myelogenous leukemia. Blood 2011 Dec 8; 118(24): 6310-6320.
4.
Heller PG, Glembotsky AC, Gandhi MJ, Cummings CL, Pirola CJ, Marta RF, et al. Low Mpl
receptor expression in a pedigree with familial platelet disorder with predisposition to acute
myelogenous leukemia and a novel AML1 mutation. Blood 2005 Jun 15; 105(12): 4664-4670.
5.
Bendl J, Stourac J, Salanda O, Pavelka A, Wieben ED, Zendulka J, et al. PredictSNP: robust and
accurate consensus classifier for prediction of disease-related mutations. PLoS computational
biology 2014 Jan; 10(1): e1003440.
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