Abstract
Background: The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (NOS1AP)is
located on chromosome 1q23.3, a candidate region for schizophrenia, autism spectrum disorders (ASD) and
obsessive-compulsive disorder (OCD). Previous genetic and functional studies explored the role of NOS1AP in these
psychiatric conditions, but only a limited number explored the sequence variability of NOS1AP.
Methods: 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).
Results: 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.
Conclusions: 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.Background replicated by Ylisaukko-oja et al., [8] who found a signifi-本文来自优.文,论-文·网原文请找腾讯752018766
The current concepts adopted by DSM-IV and ICD-10 cant linkage between patients with Asperger syndrome,
thatdefineapsychiatricdisorderasasingleentitymay known to have frequent OC symptoms [9], and 1q23.3
be misleading and hamper the identification of suscept- (D1S484, LOD score = 3.58 under dominant model). In
ibility genes. Some disorders classically considered as OCD patients a linkage at chromosome 1q23.3 was
separate conditions could be envisaged as being the phe- observed in the early-onset group (age at onset <18
notypic extremes of a continuum caused by an overlap- years) [10]. Non parametric multipoint linkage analysis
ping set of genes. Indeed, the same region on produced a maximum LOD score of 2.94 at D1S1679
chromosome 1q23.3 was detected in whole genome scans with an empirical p value equal at 0.001 after
for separate psychiatric disorders and could therefore permutations.
contain one shared susceptibility gene for these condi- Several genes located in region 1q23.3 have been stu-
tions. For schizophrenia, several linkage studies detected died, e.g. the regulator of G-protein signalling 4 gene
a significant linkage at 1q23.3 [1-6]. The same region was [11-14], the myelin protein zero like 1 gene [15], the
detected in two linkage studies in autism spectrum disor- UHMK1 gene [16], encoding for a serine/threonine pro-
ders (ASD). Buxbaum et al., [7] reported an association tein kinase, and the carboxyl-terminal PDZ ligand of
between patients with autism and obsessive-compulsive neural nitric synthase (NOS1AP)gene.Amongthese
behaviors (OCD), and D1S1677 (p value = 0.003 under genes, NOS1AP remains the most promising candidate.
multipoint nonparametric analyses). These results were Brzustowicz et al., [17] analyzed 14 microsatellites and
15 single nucleotide polymorphisms (SNPs) between
D1S1653 and D1S1679, and found a significant
* Correspondence: Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France2494