TY - JOUR T1 - Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: analysis of 78 patients from 21 families. JF - Blood Y1 - 2011 A1 - Noris, Patrizia A1 - Perrotta, Silverio A1 - Seri, Marco A1 - Pecci, Alessandro A1 - Gnan, Chiara A1 - Loffredo, Giuseppe A1 - Pujol-Moix, Núria A1 - Zecca, Marco A1 - Scognamiglio, Francesca A1 - De Rocco, Daniela A1 - Punzo, Francesca A1 - Melazzini, Federica A1 - Scianguetta, Saverio A1 - Casale, Maddalena A1 - Marconi, Caterina A1 - Pippucci, Tommaso A1 - Amendola, Giovanni A1 - Notarangelo, Lucia D A1 - Klersy, Catherine A1 - Civaschi, Elisa A1 - Balduini, Carlo L A1 - Savoia, Anna KW - Adolescent KW - Adult KW - Aged KW - Aged, 80 and over KW - Ankyrin Repeat KW - Child KW - Cohort Studies KW - Family KW - Female KW - Gene Frequency KW - Humans KW - Inheritance Patterns KW - Male KW - Middle Aged KW - Mutation KW - Pedigree KW - Thrombocytopenia KW - Transcription Factors KW - Young Adult AB -

Until recently, thrombocytopenia 2 (THC2) was considered an exceedingly rare form of autosomal dominant thrombocytopenia and only 2 families were known. However, we recently identified mutations in the 5'-untranslated region of the ANKRD26 gene in 9 THC2 families. Here we report on 12 additional pedigrees with ANKRD26 mutations, 6 of which are new. Because THC2 affected 21 of the 210 families in our database, it has to be considered one of the less rare forms of inherited thrombocytopenia. Analysis of all 21 families with ANKRD26 mutations identified to date revealed that thrombocytopenia and bleeding tendency were usually mild. Nearly all patients had no platelet macrocytosis, and this characteristic distinguishes THC2 from most other forms of inherited thrombocytopenia. In the majority of cases, platelets were deficient in glycoprotein Ia and α-granules, whereas in vitro platelet aggregation was normal. Bone marrow examination and serum thrombopoietin levels suggested that thrombocytopenia was derived from dysmegakaryopoiesis. Unexplained high values of hemoglobin and leukocytes were observed in a few cases. An unexpected finding that warrants further investigation was a high incidence of acute leukemia. Given the scarcity of distinctive characteristics, the ANKRD26-related thrombocytopenia has to be taken into consideration in the differential diagnosis of isolated thrombocytopenias.

VL - 117 IS - 24 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21467542?dopt=Abstract ER -