ACTN1 mutations lead to a benign form of platelet macrocytosis not always associated with thrombocytopenia

Michela Faleschini, Federica Melazzini, Caterina Marconi, Tania Giangregorio, Tommaso Pippucci, Elena Cigalini, Alessandro Pecci, Roberta Bottega, Ugo Ramenghi, Timo Siitonen, Marco Seri, Annalisa Pastore, Anna Savoia, Patrizia Noris

Research output: Contribution to journalArticlepeer-review


The inherited thrombocytopenias (IT) are a heterogeneous group of diseases resulting from mutations in more than 30 different genes. Among them, ACTN1-related thrombocytopenia (ACTN1-RT; Online Mendelian Inheritance in Man: 615193) is one of the most recently identified forms. It has been described as a mild autosomal dominant macrothrombocytopenia caused by mutations in ACTN1, a gene encoding for one of the two non-muscle isoforms of α-actinin. We recently identified seven new unrelated families with ACTN1-RT caused by different mutations. Two of them are novel missense variants (p.Trp128Cys and p.Pro233Leu), whose pathogenic role has been confirmed by in vitro studies. Together with the 10 families we have previously described, our cohort of ACTN1-RT now consists of 49 individuals carrying ACTN1 mutations. This is the largest case series ever collected and enabled a critical evaluation of the clinical aspects of the disease. We concluded that ACTN1-RT is the fourth most frequent form of IT worldwide and it is characterized by platelet macrocytosis in all affected subjects and mild thrombocytopenia in less than 80% of cases. The risk of bleeding, either spontaneous or upon haemostatic challenge, is negligible and there are no other associated defects, either congenital or acquired. Therefore, ACTN1-RT is a benign form of IT, whose diagnosis provides affected individuals and their families with a good prognosis.

Original languageEnglish
JournalBritish Journal of Haematology
Publication statusAccepted/In press - Jan 1 2018
Externally publishedYes


  • ACTN1 gene
  • ACTN1-related thrombocytopenia
  • macrocytosis
  • mutations
  • thrombocytopenia

ASJC Scopus subject areas

  • Hematology


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