Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia

Analysis of 78 patients from 21 families

Patrizia Noris, Silverio Perrotta, Marco Seri, Alessandro Pecci, Chiara Gnan, Giuseppe Loffredo, Nuria Pujol-Moix, Marco Zecca, Francesca Scognamiglio, Daniela De Rocco, Francesca Punzo, Federica Melazzini, Saverio Scianguetta, Maddalena Casale, Caterina Marconi, Tommaso Pippucci, Giovanni Amendola, Lucia D. Notarangelo, Catherine Klersy, Elisa Civaschi & 2 others Carlo L. Balduini, Anna Savoia

Research output: Contribution to journalArticle

139 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6673-6680
Number of pages8
JournalBlood
Volume117
Issue number24
DOIs
Publication statusPublished - Jun 16 2011

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Platelets
Thrombocytopenia
Mutation
Thrombopoietin
5' Untranslated Regions
Blood Platelets
Glycoproteins
Bone
Hemoglobins
Bone Marrow Examination
Agglomeration
Genes
Pedigree
Platelet Aggregation
Leukemia
Leukocytes
Differential Diagnosis
Thrombocytopenia chromosome breakage
Databases
Hemorrhage

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia : Analysis of 78 patients from 21 families. / Noris, Patrizia; Perrotta, Silverio; Seri, Marco; Pecci, Alessandro; Gnan, Chiara; Loffredo, Giuseppe; Pujol-Moix, Nuria; Zecca, Marco; Scognamiglio, Francesca; De Rocco, Daniela; Punzo, Francesca; Melazzini, Federica; Scianguetta, Saverio; Casale, Maddalena; Marconi, Caterina; Pippucci, Tommaso; Amendola, Giovanni; Notarangelo, Lucia D.; Klersy, Catherine; Civaschi, Elisa; Balduini, Carlo L.; Savoia, Anna.

In: Blood, Vol. 117, No. 24, 16.06.2011, p. 6673-6680.

Research output: Contribution to journalArticle

Noris, P, Perrotta, S, Seri, M, Pecci, A, Gnan, C, Loffredo, G, Pujol-Moix, N, Zecca, M, Scognamiglio, F, De Rocco, D, Punzo, F, Melazzini, F, Scianguetta, S, Casale, M, Marconi, C, Pippucci, T, Amendola, G, Notarangelo, LD, Klersy, C, Civaschi, E, Balduini, CL & Savoia, A 2011, 'Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: Analysis of 78 patients from 21 families', Blood, vol. 117, no. 24, pp. 6673-6680. https://doi.org/10.1182/blood-2011-02-336537
Noris, Patrizia ; Perrotta, Silverio ; Seri, Marco ; Pecci, Alessandro ; Gnan, Chiara ; Loffredo, Giuseppe ; Pujol-Moix, Nuria ; Zecca, Marco ; Scognamiglio, Francesca ; De Rocco, Daniela ; Punzo, Francesca ; Melazzini, Federica ; Scianguetta, Saverio ; Casale, Maddalena ; Marconi, Caterina ; Pippucci, Tommaso ; Amendola, Giovanni ; Notarangelo, Lucia D. ; Klersy, Catherine ; Civaschi, Elisa ; Balduini, Carlo L. ; Savoia, Anna. / Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia : Analysis of 78 patients from 21 families. In: Blood. 2011 ; Vol. 117, No. 24. pp. 6673-6680.
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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

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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.

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