Novel missense mutations in the glycine receptor β subunit gene (GLRB) in startle disease

► We report novel missense mutations in the GlyR β subunit gene causing startle disease. ► Mutation M177R in the extracellular domain decreases GlyR agonist affinity. ► Mutation L285R in TM2 produces spontaneously active channels. ► Mutation W310C in TM3 affects hydrophobic stacking and shows incomplete dominance. ► Mutations in GLRB have unique pathogenic mechanisms and modes of inheritance.