Publication date: Jun 21, 2025

Autism spectrum disorder (ASD) is a neurodevelopmental condition that is frequently accompanied by developmental delay and epilepsy. There is increasing evidence that genetic factors play a key role and that variations in the MARK2 gene are associated with neurodevelopmental disorders. Nevertheless, clinical reports associating MARK2 variants with human disease remain limited. Exome sequencing (ES) was performed on a patient with ASD, developmental delay, and epilepsy. Candidate variants were prioritized based on inheritance patterns, population allele frequency, and clinical relevance, following the ACMG guidelines. Sanger sequencing was used to validate the identified variant in the family. The patient is a five-year-old male who presented with ASD, epilepsy and developmental delay. The brain MRI was normal, but the EEG results showed abnormal brain activity with sharp and slow waves in the right occipital and posterior temporal regions. A frameshift variant in the MARK2 (c. 645_646insA, p. (Ala216Serfs*12)) gene was identified in the patient through ES. It was de novo and confirmed by Sanger sequencing. This study contributes to the expansion of the genotypic spectrum of MARK2-related neurodevelopmental disorders. A novel de novo frameshift variant was identified in a patient with ASD, developmental delay and epilepsy. These findings provide further evidence supporting the role of MARK2 as a disease-associated gene and highlight its potential role in neurodevelopment.

Semantics

Original Article