NBEA: Developmental disease gene with early generalized epilepsy phenotypes.

Area of Science:

• Genetics
• Neuroscience
• Developmental Biology

Background:

• The neurobeachin (NBEA) gene has been implicated as a potential candidate gene for autism spectrum disorder.
• Previous reports have identified de novo variants in NBEA within neurodevelopmental disease (NDD) cohorts.
• However, NBEA has not been comprehensively validated as a disease-causing gene, and its associated phenotypic spectrum remains undelineated.

Purpose of the Study:

• To rigorously evaluate the neurobeachin (NBEA) gene as a cause of neurodevelopmental disease (NDD).
• To delineate the clinical and phenotypic spectrum associated with de novo variants in the NBEA gene.
• To establish NBEA as a significant NDD gene.

Main Methods:

• Identification and analysis of de novo variants in the NBEA gene in a cohort of patients diagnosed with NDD.
• Clinical phenotyping of patients carrying identified NBEA variants.
• Comparison of observed phenotypes with previously described NBEA-associated features.

Main Results:

• Twenty-four de novo NBEA variants were identified in patients with NDD.
• The majority of patients presented with epilepsy, typically with onset in early childhood.
• Common seizure types included generalized seizures, such as myoclonic and atonic seizures, with a subset exhibiting a myoclonic-astatic epilepsy-like phenotype.

Conclusions:

• The identification of de novo NBEA variants in NDD patients establishes NBEA as a confirmed NDD gene.
• The study reveals a broader phenotypic spectrum for NBEA-related disorders than previously recognized.
• Epilepsy, particularly with early-onset generalized seizures, is a prominent feature of NBEA-associated neurodevelopmental disease.