title: A pedigree with autosomal dominant thrombocytopenia, red cell macrocytosis, and an occurrence of t(12:21) positive pre-B acute lymphoblastic leukemia.
abstract: Sampling and analyzing new families with inherited blood disorders are major steps contributing to the identification of gene(s) responsible for normal and pathologic hematopoiesis. Familial occurrences of hematological disorders alone, or as part of a syndromic disease, have been reported, and for some the underlying genetic mutation has been identified. Here we describe a new autosomal dominant inherited phenotype of thrombocytopenia and red cell macrocytosis in a four-generation pedigree. Interestingly, in the youngest generation, a 2-year-old boy presenting with these familial features has developed acute lymphoblastic leukemia characterized by a t(12;21) translocation. Tri-lineage involvement of platelets, red cells and white cells may suggest a genetic defect in an early multiliear progenitor or a stem cell. Functional assays in EBV-transformed cell lines revealed a defect in cell proliferation and tubulin dynamics. Two candidate genes, RUNX1 and FOG1, were sequenced but no pathogenic mutation was found. Identification of the underlying genetic defect(s) in this family may help in understanding the complex process of hematopoiesis.
authors: Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
authors: Robert
authors: R
authors: Escher
authors: Peter
authors: P
authors: Wilson
authors: Catherine
authors: C
authors: Carmichael
authors: Ram
authors: R
authors: Suppiah
authors: Marjorie
authors: M
authors: Liu
authors: Maria
authors: M
authors: Kavallaris
authors: Ping
authors: P
authors: Cannon
authors: Joelle
authors: J
authors: Michaud
authors: Hamish S
authors: HS
authors: Scott
mesh_terms: D000328:Adult; D000748:Anemia, Macrocytic / Q000235:genetics*; D002051:Burkitt Lymphoma / Q000235:genetics*; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit; D005190:Family; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D010375:Pedigree; D013921:Thrombocytopenia / Q000235:genetics*; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D009687:Nuclear Proteins; C493728:RUNX1 protein, human; D014157:Transcription Factors; C498432:ZFPM1 protein, human