title: Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: analysis of 78 patients from 21 families.
abstract: 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.
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, Pavia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Noris
authors.forename: Silverio
authors.initials: S
authors.lastname: Perrotta
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
authors.forename: Chiara
authors.initials: C
authors.lastname: Gnan
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Loffredo
authors.forename: Nuria
authors.initials: N
authors.lastname: Pujol-Moix
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.forename: Francesca
authors.initials: F
authors.lastname: Scognamiglio
authors.forename: Daniela
authors.initials: D
authors.lastname: De Rocco
authors.forename: Francesca
authors.initials: F
authors.lastname: Punzo
authors.forename: Federica
authors.initials: F
authors.lastname: Melazzini
authors.forename: Saverio
authors.initials: S
authors.lastname: Scianguetta
authors.forename: Maddalena
authors.initials: M
authors.lastname: Casale
authors.forename: Caterina
authors.initials: C
authors.lastname: Marconi
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pippucci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Amendola
authors.forename: Lucia D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Elisa
authors.initials: E
authors.lastname: Civaschi
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Balduini
authors.forename: Anna
authors.initials: A
authors.lastname: Savoia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017089:Ankyrin Repeat / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D005190:Family; D005260:Female; D005787:Gene Frequency; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D010375:Pedigree; D013921:Thrombocytopenia / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D055815:Young Adult
chemical_list: D014157:Transcription Factors