A novel microduplication in INPP5A segregates with schizophrenia spectrum disorder in the family of a patient with both childhood onset schizophrenia and autism spectrum disorder

Childhood-Onset Schizophrenia (COS) is a very rare and severe psychiatric disorder defined by adult schizophrenia symptoms occurring before the age of 13. We report microduplication in 10q26.3 region including part Inositol Polyphosphate-5-Phosphatase A (INPP5A) gene that segregates with Spectrum Disorders (SSDs) family female patient affected both COS Autism Disorder (ASD). Phenotyping genotyping (including CGH-array) were performed for mother, healthy sister, child according to GenAuDiss protocol (NCT02565524). The duplication size 324 kb present her mother SSD, but not patient's sister. INPP5A encodes membrane-associated 43 kDa type I inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. This protein found mouse human brains we its Drosophila homologue 5PtaseI specifically expressed central nervous system. Hydrolyzed products from InsP3 5-phosphatases mobilize intracellular calcium, which relevant dendritic spine morphogenesis neurons altered ASD. These may constitute arguments favor this alteration pathophysiology COS.