The subject of this report is a newly described neurodevelopmental disorder associated with the human gene MRTFB; MRTFB encodes a protein that acts as a transcriptional coactivator. There is a single orthologous gene in Drosophila, Mrtf. Dmel\Mrtf is also orthologous to the human genes MRTFA and MYOCD. A small number of genetic reagents have been generated for Dmel\Mrtf, including RNAi-targeting constructs and alleles caused by insertional mutagenesis.
Two de novo variants associated with this disorder have been identified: MRTFB:p.Ala91Pro and MRTFB:p.Arg104Gly (see the 'Disease-Implicated Variants' table below); both map to the actin-binding domain of the MRTFB protein.
In the Drosophila disease model, UAS constructs carrying wild-type or variants of the human Hsap\MRTFB gene have been expressed in different tissues. The variants appear to function as gain-of-function mutations in these genetic assays. Increased transcriptional activity and changes in the organization of the actin cytoskeleton are observed.
[updated Sep. 2023 by FlyBase; FBrf0222196]
Two patients described with mild dysmorphic features, intellectual disability, global developmental delays, speech apraxia, and impulse control issues (Andrews, et al., 2023; pubmed:37013900; FBrf0256703).
In the 2 cases described, the implicated MRTFB variants appear to have originated de novo (Andrews, et al., 2023; pubmed:37013900; FBrf0256703).
MRTFB encodes a protein that acts as a transcriptional coactivator; plays a role in regulation of striated muscle tissue development. [Gene Cards, MRTFB; 2023.09.26]
Many to one: 3 human genes to 1 Drosophila gene.
Moderate-scoring ortholog of human MRTFB, MRTFA, and MYOCD (1 Drosophila to 3 human).
