Characterization of a rare Unverricht–Lundborg disease mutation

• Cystatin B mutation c.66G > A is undoubtedly rare.
• Protein fractionation demonstrated that cystatin B is mislocated in the mutant cells.
• Mislocation of cystatin B may be the underlying cause of Unverricht–Lundborg.

Cystatin B (CSTB) gene mutations cause Unverricht–Lundborg disease (ULD), a rare form of myoclonic epilepsy. The previous identification of a Portuguese patient, homozygous for a unique splicing defect (c.66G > A; p.Q22Q), provided awareness regarding the existence of variant forms of ULD. In this work we aimed at the characterization of this mutation at the population level and at the cellular level. The cellular fractionation studies here carried out showed mislocalization of the protein and add to the knowledge on this disease.