Connecting genotype and phenotype in CACNA1A-associated disorders

Mutations in the calcium channel gene CACNA1A are linked to diverse neurological and developmental disorders. This clinical diversity, along with complex protein-level consequences, makes it hard to interpret variants' impacts. Erkin Kurganov, Lei Cui, Nikita Budnik, Jen Pan, and collaborators have now characterized the neuronal activity changes caused by 42 de novo CACNA1A variants in human neurons. They found that all variants but one affected calcium channel function and the excitability of human neurons and, in conjunction with clinical data, correlated variants with distinct clinical outcomes. Their study, published in Science Translational Medicine, should guide the development of new treatments for CACNA1A-associated disorders.