title: Clinical phenotype of germline RUNX1 haploinsufficiency: from point mutations to large genomic deletions.
abstract: Germline RUNX1 mutations result in a rare autosomal dominant condition characterized by qualitative and quantitative platelet defects and predisposition to the development of myeloid malignancies (familial platelet disorder with propensity to acute myeloid leukaemia, FPD/AML). Only 13 pedigrees have previously been described so far. We report on two novel germline RUNX1 mutations: (1) an out-of-frame 8 bp heterozygous deletion (c.442_449del) in an FPD/AML pedigree and (2) a de novo 3.5 Mb deletion in the 21q22.11.21q22.12 region encompassing the RUNX1 gene in a mentally retarded female patient with short stature and thrombocytopenia. Interestingly, a similar de novo submicroscopic deletion has been recently reported in the literature in a mentally retarded patient. Mental retardation is one of the most common disorders and primary causes of thrombocytopenia are rare. When occurring together, these features should prompt to test for 21q22 deletion for comprehensive genetic counselling and clinical management.
authors.affiliation: Laboratoire de Génétique, Centre Hospitalier Universitaire de Nancy Brabois, Nancy Université, EA4002, France.
authors.forename: Mylène
authors.initials: M
authors.lastname: Béri-Dexheimer
authors.forename: Véronique
authors.initials: V
authors.lastname: Latger-Cannard
authors.forename: Christophe
authors.initials: C
authors.lastname: Philippe
authors.forename: Céline
authors.initials: C
authors.lastname: Bonnet
authors.forename: Pascal
authors.initials: P
authors.lastname: Chambon
authors.forename: Virginie
authors.initials: V
authors.lastname: Roth
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Grégoire
authors.forename: Pierre
authors.initials: P
authors.lastname: Bordigoni
authors.forename: Thomas
authors.initials: T
authors.lastname: Lecompte
authors.forename: Bruno
authors.initials: B
authors.lastname: Leheup
authors.forename: Philippe
authors.initials: P
authors.lastname: Jonveaux
mesh_terms: D001791:Blood Platelet Disorders / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D015894:Genome, Human; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D013921:Thrombocytopenia / Q000235:genetics*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human; D004247:DNA