PPP2R1A-Related Neurodevelopmental Disorder: The First Korean Case with a Novel Variant of PPP2R1A and Literature Review.

In 2015, germline mutations in PPP2R1A were found to cause neurodevelopmental disorders (NDDs). To date, fewer than 50 cases of PPP2R1A-related NDDs have been reported. Here, we report the first Korean case of PPP2R1A-related NDD harboring a novel de novo missense PPP2R1A variant with previously unreported clinical features. The proband, a 12-month-old female, presented with developmental delay, intractable epilepsy, microcephaly, and feeding difficulties. Brain magnetic resonance imaging showed a Dandy-Walker continuum with corpus callosum hypoplasia, periventricular leukomalacia, and brainstem and diffuse cerebral atrophy. Next-generation sequencing-based targeted gene panel testing for NDDs revealed a novel heterozygous missense variant of PPP2R1A:c.650A>G, p.(Gln217Arg). Sanger sequencing confirmed it as de novo, as neither parent carried this variant. These findings expand the phenotypic and genotypic spectra of PPP2R1A variants.