Expanding the Allelic spectrum in ATP1A3-related disorders with 3 novel mutations and clinic features

To describe the complex phenotype of ATP1A3 and second to report new mutation of ATP1A3.

This is a retrospective chart review of 7 patients who was diagnosed with ATP1A3 mutation based on whole exome sequencing (WES) result and the following information were collected; age, age of onset, developmental ability, seizure type, family history, MRI, WES report. The data collection started a year ago January 2021 in King Faisal Specialist Hospital and Research Centre, Riyadh, KSA. This has been cleared for publication by the Office of Research Affairs, and the Publication Number is 2225429.

Five females and 2 males had onset ages of 0-3 years (mean=18 months). All had some degree of intellectual dysfunction, 6 had seizures (85%), 4 had neurologic abnormalities, 1 had autistic features and one had mild dystonia.

Our small-cohort observations confirm that ATP1A3 mutations express a wide range of phenotypes, usually including some degree of cognitive-behavioral dysfunction (100% of patients), seizures (85% of patients), and AHC (71% of patients). Moreover, they further expand the evolving allelic spectrum of these disorders by identifying 3 novel mutations.