Cystic cerebellar dysplasia and biallelic LAMA1 mutations: a lamininopathy associated with tics, obsessive compulsive traits and myopia due to cell adhesion and migration defects

Laminins are proteins that form a major component of basement membranes and extracellular matrix in human tissues. We have performed clinical and neuropsychiatric evaluation, and molecular analysis in patients with mutations in the LAMA1 gene that codes for the protein laminin-α1. We investigated the consequence of mutations in LAMA1 using nerve cells derived from stem cells and patients’ skin cells. Patients had cyctic cerebellar dysplasia, myopia, and retinal dystrophy, obsessive compulsive behaviors, tics, and anxiety. Skin cells had impaired adhesion, reduced migration, and abnormal morphology. Human neuronal cells without laminin-α1 showed abnormal cellular extension formation marking these cells potentially useful tools for disease modeling and drug discovery. (By Dr. Meral Gunay-Aygun, http://jmg.bmj.com/content/early/2016/01/13/jmedgenet-2015-103416 )