BRWD3 – Childhood Epilepsy with Centrotemporal Spikes

The X-linked gene BRWD3 encodes a bromodomain-and-WD repeat–containing protein implicated in neurodevelopment. In a cohort of 47 unrelated patients with childhood epilepsy with centrotemporal spikes, array CGH and qPCR detected a rare BRWD3-disrupting microdeletion in one proband (PMID:24372385). No segregation data are available, and this represents the sole CNV event in BRWD3 among RE cases.

Supporting functional evidence arises from idiopathic partial epilepsy without intellectual disability, where two recurrent missense variants in BRWD3, c.836C>T (p.Thr279Ile) and c.4234A>C (p.Ile1412Leu), localized to WD40 and bromodomains, were predicted damaging and alter hydrogen bonding (PMID:36514184). All variants were maternally inherited, and carriers responded well to antiepileptics. While no in vivo or cellular rescue studies exist, domain-specific impacts on protein function suggest a seizure-predisposing mechanism. Overall, evidence for BRWD3 in RE is limited, warranting expanded CNV and sequencing studies to clarify its role. Key take-home: inclusion of BRWD3 in genetic testing panels may identify rare CNVs or missense changes contributing to RE susceptibility.

References

• Epilepsia • 2014 • A subset of genomic alterations detected in rolandic epilepsies contains candidate or known epilepsy genes including GRIN2A and PRRT2 PMID:24372385
• CNS neuroscience & therapeutics • 2023 • Variants in BRWD3 associated with X-linked partial epilepsy without intellectual disability PMID:36514184

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