TY - JOUR
T1 - Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: Analysis of 78 patients from 21 families
AU - Noris, Patrizia
AU - Perrotta, Silverio
AU - Seri, Marco
AU - Pecci, Alessandro
AU - Gnan, Chiara
AU - Loffredo, Giuseppe
AU - Pujol-Moix, Nuria
AU - Zecca, Marco
AU - Scognamiglio, Francesca
AU - De Rocco, Daniela
AU - Punzo, Francesca
AU - Melazzini, Federica
AU - Scianguetta, Saverio
AU - Casale, Maddalena
AU - Marconi, Caterina
AU - Pippucci, Tommaso
AU - Amendola, Giovanni
AU - Notarangelo, Lucia D.
AU - Klersy, Catherine
AU - Civaschi, Elisa
AU - Balduini, Carlo L.
AU - Savoia, Anna
PY - 2011/6/16
Y1 - 2011/6/16
N2 - 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. © 2011 by The American Society of Hematology.
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. © 2011 by The American Society of Hematology.
U2 - 10.1182/blood-2011-02-336537
DO - 10.1182/blood-2011-02-336537
M3 - Article
VL - 117
SP - 6673
EP - 6680
JO - Blood
JF - Blood
SN - 0006-4971
IS - 24
ER -