Novel Perspectives on ATP8A2 Regulation: Evidence for Parental Imprinting and Chimeric Transcript Formation

Abstract

<b>Background</b>: Parental imprinting plays a crucial role in epigenetic regulation and is increasingly recognized for its involvement in neurodevelopmental disorders. Although <i>ATP8A2</i> is considered a non-imprinted gene; However, the marked phenotypic variability observed across related disorders suggests that additional regulatory layers may influence its expression. <b>Methods</b>: We investigated the imprinting-like status of <i>ATP8A2</i> through functional analyses of a splicing variant (c.1580-3C>G) identified in a patient diagnosed with Cerebellar Ataxia, Mental Retardation, and Disequilibrium syndrome type 4 (CAMRQ4). Sanger sequencing was used to assess allelic expression and identify aberrant transcripts. <b>Results</b>: Our analyses revealed an allelic expression imbalance suggestive of parental imprinting of <i>ATP8A2</i>. Moreover, Sanger sequencing led to the identification of a novel <i>ATP8A2</i>-<i>RAB3GAP2</i> chimeric transcript, pointing to a previously unreported transcriptional event, the functional relevance of which remains to be determined. <b>Conclusions</b>: These findings indicate that <i>ATP8A2</i> may be subject to imprinting-like regulation and involved in atypical splicing events with unknown significance. This highlights the need for further investigation into the epigenetic and transcriptional complexity of <i>ATP8A2</i>-related neurodevelopmental disorders.