In a small subset of patients, apparently balanced structural chromosome rearrangements may associate with neurocognitive problems ranging from mild (ADHD, dyslexia) to severe (within the autism spectrum disorders and intellectual disability). Here, we use low coverage massive parallel whole genome sequencing and microarray analysis to identify hemizygous loss of CTNND2 in three individuals from two unrelated families who show borderline to moderate intellectual dysfunction and specific problems with reading. The gene was first identified by whole genome sequencing in a carrier of two balanced reciprocal chromosomal translocations, t(1;8)(p22;q24) and t(5;18)(p15;q11). We then demonstrate an effect of CTNND2 polymorphisms on normal reading ability and normal variability in white matter volume. Finally, we show that the loss of CTNND2 function in zebrafish results in ectopic neurons, indicative of abnormal neuronal migration. Our work indicates that isolated CTNND2 mutations lead to learning difficulties, in particular reading disability. (By Dr. Anna Lindstrand, http://jmg.bmj.com/content/early/2014/12/03/jmedgenet-2014-102757 )