Using DNA sequencing to detect rare genetic disorders underlying childhood-onset schizophrenia

Schizophrenia is a chronic highly heritable mental health disorder affecting ~1% of the population. Symptoms of schizophrenia usually appear in early adulthood, and it is referred to as adult-onset schizophrenia (AOS). However, very rare and severe form of this disease occurs before the age of 13 and it is known as childhood-onset schizophrenia (COS). Recent studies demonstrated a higher burden of de novo variants in COS patients compared to those with AOS. These findings underscore the need for further research into the impact of de novo variants in the origins and development of COS. Here we analyze Whole Exome Sequencing data from a cohort of COS trios and report 12 de novo SNVs. Among the discovered variants, 2 are highlighted as being of potential clinical significance. These missense variants affect 2 genes, RTN1 and KCNB1, that are expressed in brain and involved in neurological pathways. In addition, these genes have already been reported in patients with neurological and psychiatric conditions such as autism spectrum disorder, intellectual disability and motor dysfunction, which are comorbidities commonly present in patients with COS.