Familial Macrothrombocytopenia Due to a Double Mutation in Cis in the Alpha-Actinin 1 Gene (ACTN1), Previously Considered to Be Chronic Immune Thrombocytopenic Purpura

Pediatr Blood Cancer. 2018 Dec;65(12):e27418. doi: 10.1002/pbc.27418. Epub 2018 Aug 19.


Congenital thrombocytopenia can easily be misdiagnosed as immune thrombocytopenic purpura, as is illustrated by this case of a woman and her two children. Doubts arose when steroid/IVIG therapy failed in the mother and the thrombocytopenia in the children persisted. By means of next-generation sequencing, two missense variants in cis in the ACTN1 gene of the affected family members were identified, both of unknown significance. We conclude, after further analysis of these mutations with, among others, in silico prediction tools, that the thrombocytopenia has a genetic cause, in particular the ACTN1 mutations, and is not immune mediated.

Keywords: ACTN1; ITP; actinin 1; congenital macrothrombocytopenia; next-generation sequencing.

Publication types

  • Case Reports

MeSH terms

  • Actinin / genetics*
  • Child
  • Diagnostic Errors
  • Female
  • Humans
  • Male
  • Mutation, Missense
  • Purpura, Thrombocytopenic, Idiopathic / diagnosis
  • Thrombocytopenia / diagnosis
  • Thrombocytopenia / genetics*


  • ACTN1 protein, human
  • Actinin