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

Background

Parental imprinting plays a crucial role in epigenetic regulation and is increasingly recognized for its involvement in neurodevelopmental disorders. Although ATP8A2 is considered a non-imprinted gene; However, the marked phenotypic variability observed across related disorders suggests that additional regulatory layers may influence its expression.

Methods

We investigated the imprinting-like status of ATP8A2 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.

Results

Our analyses revealed an allelic expression imbalance suggestive of parental imprinting of ATP8A2. Moreover, Sanger sequencing led to the identification of a novel ATP8A2-RAB3GAP2 chimeric transcript, pointing to a previously unreported transcriptional event, the functional relevance of which remains to be determined.

Conclusions

These findings indicate that ATP8A2 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 ATP8A2-related neurodevelopmental disorders.