CACNB4 – Juvenile Myoclonic Epilepsy

CACNB4 has been implicated in juvenile myoclonic epilepsy through identification of a premature‐termination mutation c.1444C>T (p.Arg482Ter) in one patient (PMID:10762541), with no additional segregating relatives and absence in controls. In Xenopus laevis oocytes, c.1444C>T (p.Arg482Ter) caused a modest acceleration of calcium current inactivation, mirroring the mouse lethargic absence epilepsy phenotype (PMID:10762541). Separately, a Cys104Phe missense variant (c.311G>T (p.Cys104Phe)) was reported in familial generalized epilepsy and episodic ataxia (PMID:10762541). However, linkage analysis in a consanguineous Tunisian pedigree with four affected siblings failed to identify CACNB4 coding variation (PMID:20378313). Overall, limited genetic evidence (one JME case) and modest functional effects support a Limited gene‐disease association. Additional cohort studies and in vivo models are needed to clarify CACNB4’s role. Key take-home: CACNB4 variants remain candidate risk factors for JME but lack sufficient evidence for clinical diagnosis.

References

• American journal of human genetics • 2000 • Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. PMID:10762541
• Epilepsy research • 2010 • Genetic linkage study of an autosomal recessive form of juvenile myoclonic epilepsy in a consanguineous Tunisian family. PMID:20378313

Evidence Based Scoring (AI generated)