Autistic features and/or stereotypy has been observed in a subset of individuals with both PPP3CA-associated disorders (Myers et al., 2017; Mizuguchi et al., 2018; Panneerselvam et al., 2021). Genotype-phenotype correlation of 5 novel patients and 16 previously unpublished patients with PPP3CA variants in Panneerselvam et al., 2021 found that while autistic features were overall a commonly observed phenotype in individuals with PPP3CA variants (11/20, 55%), they were more frequently observed in individuals with missense variants in the catalytic domain (7/9, 78%) or the auto-inhibitory domain (2/3, 67%) of PPP3CA compared to individuals with truncating variants in the regulatory domain of the protein (1/7, 14%). Mizuguchi et al., 2018 had previously shown that missense variants in the catalytic domain of PPP3CA exhibit loss-of-function properties, whereas missense variants in the auto-inhibitory domain display gain-of-function properties. A rare de novo missense variant in PPP3CA has also been identified in an ASD proband from the Autism Sequencing Consortium in Satterstrom et al., 2020.
Molecular Function
The protein encoded by the PPP3CA gene is a calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca2+-mediated signals. Heterozygous variants in this gene are responsible for two distinct disorders: arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development (ACCIID; OMIM 618265), and developmental and epileptic encephalopathy-91 (DEE91; OMIM 617711).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De Novo Mutations in PPP3CA Cause Severe Neurodevelopmental Disease with Seizures
