Submission Details

Autosomal dominant

09/03/2019

The ACTB gene was first reported in relation to autosomal dominant juvenile onset dystonia in 2006 (16685646: Procaccio et al. 2006). Evidence supporting this gene-disease relationship includes case-level data and experimental data. A single recurrent missense variant in this gene has been reported in five unrelated cases from five reports. At least one case was confirmed as de novo inheritance, with another family showing inheritance of the variant in an affected daughter from her affected mother (16685646: Procaccio et al. 2006; 28487785: Conboy et al. 2017; 27862284: Eggink et al. 2017; 28849312: Zech et al. 2017; 29788902: Skogseid et al. 2018). The mechanism for disease is unknown. Of note, this gene has also been implicated in Baraitser–Winter Cerebrofrontofacial syndrome and ACTB-related syndromic thrombocytopenia. These will be assessed separately. This gene-disease relationship is supported by a knockout mouse model which recapitulates the progressive sensorineural hearing loss phenotype observed patients. Beta actin plays a specific role in maintenance of sterocilia of the inner ear, loss of beta actin in the knockout mice specifically leads to the degeneration of the stereocilia of the outer hair cells (30012594: Patrinostro et al. 2018). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.

28487785 16685646 29788902 27862284 28849312 30012594