Mutation screening of NOS1AP gene in a large sample of psychiatric patients and controls

We analyzed the coding sequence of NOS1AP in a large population (n = 280), including patients with schizophrenia (n = 72), ASD (n = 81) or OCD (n = 34), and in healthy volunteers controlled for the absence of personal or familial history of psychiatric disorders (n = 93).Two non-synonymous variations, V37I and D423N were identified in two families, one with two siblings with OCD and the other with two brothers with ASD. These rare variations apparently segregate with the presence of psychiatric conditions.Coding variations of NOS1AP are relatively rare in patients and controls. Nevertheless, we report the first non-synonymous variations within the human NOS1AP gene that warrant further genetic and functional investigations to ascertain their roles in the susceptibility to psychiatric disorders.The current concepts adopted by DSM-IV and ICD-10 that define a psychiatric disorder as a single entity may be misleading and hamper the identification of susceptibility genes. Some disorders classically considered as separate conditions could be envisaged as being the phenotypic extremes of a continuum caused by an overlapping set of genes. Indeed, the same region on chromosome 1q23.3 was detected in whole genome scans for separate psychiatric disorders and could therefore contain one shared susceptibility gene for these conditions. For schizophrenia, several linkage studies detected a significant linkage at 1q23.3 [1-6]. The same region was detected in two linkage studies in autism spectrum disorders (ASD). Buxbaum et al., [7] reported an association between patients with autism and obsessive-compulsive behaviors (OCD), and D1S1677 (p value = 0.003 under multipoint nonparametric analyses). These results were replicated by Ylisaukko-oja et al., [8] who found a significant linkage between patients with Asperger syndrome, known to have frequent OC symptoms [9], and 1q23.3 (D1S484, LOD score = 3.58 under dominant model). In OCD patients a linkage at chromosome 1q23.3 was observe