Skip to Main content Skip to Navigation
Journal articles

Novel ACTN1 variants in cases of thrombocytopenia

Abstract : The ACTN1 gene has been implicated in inherited macrothrombocytopenia. To decipher the spectrum of variants and phenotype of ACTN1-related thrombocytopenia, we sequenced the ACTN1 gene in 272 cases of unexplained chronic or familial thrombocy-topenia. We identified 15 rare, monoallelic, nonsynonymous and likely pathogenic ACTN1 variants in 20 index cases from 20 unrelated families. Thirty-one family members exhibited thrombocytopenia. Targeted sequencing was carried out on 12 affected relatives, which confirmed presence of the variant. Twenty-eight of 32 cases with monoallelic ACTN1 variants had mild to no bleeding complications. Eleven cases harbored 11 different unreported ACTN1 variants that were monoallelic and likely pathogenic. Nine variants were located in the α-actinin-1 (ACTN1) rod domain and were predicted to hinder dimer formation. These variants displayed a smaller increase in platelet size compared with variants located outside the rod domain. In vitro expression of the new ACTN1 variants induced actin network disorganization and led to increased thickness of actin fibers. These findings expand the repertoire of ACTN1 variants associated with thrombocytopenia and highlight the high frequency of ACTN1-related thrombocytopenia cases. The rod domain, like other ACTN1 functional domains, may be mutated resulting in actin disorganization in vitro and thrombocytopenia with normal platelet size in most cases.
Document type :
Journal articles
Complete list of metadata

Cited literature [31 references]  Display  Hide  Download
Contributor : Annick Prémilleux Connect in order to contact the contributor
Submitted on : Monday, April 27, 2020 - 6:43:58 PM
Last modification on : Friday, August 5, 2022 - 10:49:13 AM


Publication funded by an institution


Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License



Anne Vincenot, Paul Saultier, Shinji Kunishima, Marjorie Poggi, Marie-Françoise Hurtaud-Roux, et al.. Novel ACTN1 variants in cases of thrombocytopenia. Human Mutation, Wiley, 2019, 40 (12), pp.2258-2269. ⟨10.1002/humu.23840⟩. ⟨hal-02556150⟩



Record views


Files downloads