ACTL6B dominant

Molecular characteristics

The ACTL6B gene encodes a component of the neuron-specific BAF (nBAF) complex in postmitotic neurons. The nBAF complex has a role in chromatin remodelling and histone acetylation, which regulates gene expression during development, particularly in the process of dendritic outgrowth. This complex also contains BRG1 (SMARCA4; 603254) and BRM (SMARCA2; 600014).

Nine of these ten unrelated individuals had the identical de novo c.1027G>A (p.Gly343Arg) mutation. Human-derived neurons were generated that recaptured ACTL6B expression patterns in development from progenitor cell to post-mitotic neuron, validating the use of this model. Engineered knock-out of ACTL6B in wild-type human neurons resulted in profound deficits in dendrite development, a result recapitulated in two individuals with different bi-allelic mutations, and reversed on clonal genetic repair or exogenous expression of ACTL6B.