BRWD3 – West syndrome

BRWD3 (HGNC:17342) has emerged as a candidate X-linked gene for infantile spasms in unexplained West syndrome. In a cohort of 18 unexplained West syndrome patients, trio-based whole-exome sequencing identified hemizygous BRWD3 variants in two unrelated male probands (2/14) (PMID:25877686), with no additional segregation data reported. No recurrent or founder variants have been described to date.

Functional assessment in a separate idiopathic partial epilepsy cohort revealed missense BRWD3 variants (e.g., c.836C>T (p.Thr279Ile)) within WD40 and bromodomains that are predicted to disrupt hydrogen bonding and protein function (PMID:36514184). However, disease-specific functional assays or rescue experiments in neuronal models of infantile spasms are lacking.

Overall evidence linking BRWD3 to West syndrome is limited: only two hemizygous probands without segregation or functional confirmation in West syndrome cases have been reported. Further studies with additional unrelated families, segregation analysis, and disease-relevant functional validation are required. Key Take-home: BRWD3 is a candidate gene for X-linked West syndrome pending confirmation.

References

• Human genetics • 2015 • Genomic analysis identifies candidate pathogenic variants in 9 of 18 patients with unexplained West syndrome. PMID:25877686
• CNS neuroscience & therapeutics • 2023 • Variants in BRWD3 associated with X-linked partial epilepsy without intellectual disability. PMID:36514184

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