BCOR variants are associated with X-linked recessive partial epilepsy.

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• The BCOR gene encodes a corepressor of BCL6 and is crucial for fetal development.
• BCOR mutations have been linked to oculofaciocardiodental syndrome (OFCD).
• The role of BCOR in neurological disorders, particularly epilepsy, is not well understood.

Purpose of the Study:

• To investigate the role of BCOR gene variants in partial epilepsy.
• To identify potential genetic factors contributing to neurological disorders.

Main Methods:

• Whole-exome sequencing was performed on 323 individuals with partial epilepsy.
• Analysis of BCOR variants and comparison with control populations (healthy Chinese volunteers and gnomAD).
• Computational modeling was used to assess the impact of variants on protein structure and stability.

Main Results:

• Seven hemizygous missense BCOR variants were identified in seven patients with partial epilepsy.
• Patients presented with varied seizure types, cortical dysplasia, and mild developmental delay, but all achieved seizure freedom.
• The frequency of BCOR variants was significantly higher in the epilepsy cohort than in controls.
• Computational modeling suggested that the identified variants cause structural impairment in the BCOR protein.
• Missense BCOR variants were associated with partial epilepsy in an X-linked recessive (XLR) pattern, contrasting with X-linked dominant (XLD) patterns in OFCD.

Conclusions:

• BCOR is a potential candidate pathogenic gene for partial epilepsy, with or without developmental delay.
• Genotype-phenotype correlations provide insights into the mechanisms underlying phenotypic variations in BCOR-related disorders.