Gene Mutations and Cognitive Delay

Abstract

We congratulate T. Walsh et al. for a beautifully designed and executed study (“Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia,” Reports, 25 April, p. 539). The demonstration that the frequency of gene deletions and duplications is elevated in schizophrenia as well as in autism and many forms of mental retardation must raise suspicions that such genomic variants are not really specific for a particular disease. Buried in the Supporting Online Material is the astonishing fact that 47% of the patients with poor cognitive function (IQ < 80) had these variants, compared with only 11% of the patients with normal IQ. Poor cognitive function is a common feature of these developmental disorders and is associated with similar anatomical anomalies across a range of disorders (1–3). Perhaps genomic deletions and duplications have a nonspecific effect—restricting the flexibility of coping responses during development, constraining neuroplasticity, and rendering cognitive function more dependent on intrinsic neurobiology.