Reassessment of Rare TUBA4A Variants in Patients with Myopathy and Neurodevelopmental Features

INTRODUCTION & METHODS
TUBA4A variants are recognized in ClinGen and gene panels for adult-onset amyotrophic lateral sclerosis (ALS) & thrombocytopenia. However, recent publications have reported variants present in children with wider phenotypes. Review of internal genome and exome sequencing (WGS/WES) data for patients with unsolved phenotypes overlapping with myopathy or neurodevelopmental features uncovered 4 rare (AF<0.0001) de novo variants in TUBA4A for deeper review and reconsideration of pathogenicity. We present the evidence supporting these variant associations with pediatric myopathy and discuss the in silico data supporting future investigations of their putative pathogenic mechanisms