CACNB3 defects are associated with infantile idiopathic nystagmus

Infantile nystagmus is a common neuro-ophthalmological disorder that presents as early-onset involuntary oscillations of the eyes. Here, we report a novel genotype-phenotype correlation that associates sequence alterations in the Calcium Voltage-Gated Channel Auxiliary Subunit Beta 3 (CACNB3) gene, encoding the CaVβ3 protein, with idiopathic infantile nystagmus. Linkage analysis, whole exome and Sanger sequencing identified a homozygous missense mutation (c.316G>C) in CACNB3 co-segregating with idiopathic infantile nystagmus. Our calcium imaging experiments suggest that the p.Gly106Arg mutation in the Src homology 3 domain of CaVβ3 may impair voltage-gated calcium channel function at the plasma membrane and may increase ligand-triggered inositol trisphosphate receptor mediated calcium release at the endoplasmic reticulum. Co-localisation studies indicate reduced plasma membrane localisation of the calcium channel. We propose CACNB3 to be a novel gene associated with idiopathic infantile nystagmus. Our findings point towards an important role of calcium-signaling in idiopathic infantile nystagmus and may contribute to deciphering its aetiology.