EFHC1 – Epilepsy

Heterozygous EFHC1 variants were identified in a targeted exome study of 63 Chinese epilepsy trios, with pathogenic or likely pathogenic alleles in 15 of 63 families (PMID:28074849). A de novo EFHC1 variant, c.1504C>T (p.Arg502Trp), was reported in one case of idiopathic generalized epilepsy (PMID:36842888). No additional segregation data were described.

Functional and linkage analysis in juvenile myoclonic epilepsy failed to detect pathogenic EFHC1 mutations in 18 linked Dutch families or in 100 unrelated patients, and no case–control association was observed (PMID:17054699).

Integration of the limited identification of EFHC1 variants in unrelated epilepsy cohorts and the absence of supportive segregation or consistent functional confirmation supports a Limited clinical validity for EFHC1 in broad epilepsy diagnosis. Key take-home: EFHC1 testing may inform individual cases but currently lacks robust evidence for routine diagnostic use.

References

• Scientific reports • 2017 • Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing. PMID:28074849
• Seizure • 2024 • Clinical application of trio-based whole-exome sequencing in idiopathic generalized epilepsy. PMID:36842888
• Epilepsia • 2006 • Heterogeneity at the JME 6p11-12 locus: absence of mutations in the EFHC1 gene in linked Dutch families. PMID:17054699

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