A Mild Neurodevelopmental Phenotype Associated with a Novel BRAT1 Variant: Expanding Genotype-Phenotype Correlations

Background:BRAT1-related disorders constitute a continuous neurodevelopmental spectrum ranging from rigidity and multifocal seizure syndrome, lethal neonatal form (RMFSL) to milder phenotypes characterized by cerebellar involvement and variable developmental impairment. Genotype-phenotype correlations remain incompletely defined, particularly for missense variants that may retain residual function.

Objectives

To characterize clinical and molecular findings in a patient with a mild BRAT1-related phenotype.

Methods

An 18-year-old boy underwent clinical, neuroradiological, neurophysiological, and genetic evaluations. Exome sequencing with in silico filtering on an ataxia gene panel and parental segregation analysis was performed. BRAT1 protein expression was assessed by Western blot analysis in patient-derived fibroblasts.