HESX1 is a paired-like homeodomain transcription factor that functions as a repressor of PROP1-mediated gene stimulation. Mutations in HESX1 have been implicated in cases of septooptic dysplasia and congenital hypopituitarism. All mutations in HESX1 identified to date have resulted in impaired DNA binding and defective HESX1 action. We have identified a novel HESX1 mutation in genomic nucleotide position 1684 (g.1684delG), which results in a mutant protein with increased DNA binding. In turn, this mutation causes increased repression of PROP1-dependent gene activity. These data suggest that enhancement of transcriptional repression during pituitary organogenesis is a novel mechanism for the development of congenital pituitary disorders.

Oxytocin (OT) and arginine vasopressin (AVP) are two small, related neuropeptide hormones found in many mammalian species, including humans. Dysregulation of these neuropeptides have been associated with changes in behavior, especially social interactions. We review how the OT and AVP systems have been investigated in Autism Spectrum Disorder (ASD), Prader–Willi Syndrome (PWS), Williams Syndrome (WS) and Fragile X syndrome (FXS). All of these neurodevelopmental disorders (NDD) are marked by social deficits. While PWS, WS and FXS have identified genetic mutations, ASD stems from multiple genes with complex interactions. Animal models of NDD are invaluable for studying the role and relatedness of OT and AVP in the developing brain. We present data from a FXS mouse model affecting the fragile X mental retardation 1 (Fmr1) gene, resulting in decreased OT and AVP staining cells in some brain regions. Reviewing the research about OT and AVP in these NDD suggests that altered OT pathways may be downstream from different etiological factors and perturbations in development. This has implications for ongoing studies of the therapeutic application of OT in NDD.

Some copy number variants (CNVs) are strongly implicated in both schizophrenia and autism spectrum disorders (ASDs). Childhood-onset schizophrenia (COS) occurs rarely with 0.1 – 1% of all schizophrenia diagnoses manifesting before age 10. 3q29 deletions are associated with both autism and schizophrenia, and are rare - the frequency of the deletion estimated to be 1 in 1750 in developmental disorders. Only one patient with a 3q29 deletion was identified out of the first 1174 families with ASDs included in the Simons Simplex Collection (SSC). We report on detailed clinical findings for this patient with a de novo 3q29 deletion who, as a young child, developed a very rare overlap of symptoms of both autism and early onset psychosis. His ASD was first diagnosed at the age of 4 years and his psychotic symptoms began at 5 years old. This is only the second case reported thus far of this rare event of co-occurring autism and very early onset psychosis in a child with a 3q29 deletion. It is also the earliest case of a child with autism developing comorbid psychosis - manifesting by the age of 5 years.

CD38 encodes a ligand in the oxytocin signaling pathway. Some single nucleotide polymorphisms in this gene have been associated with low serum oxytocin levels in autism spectrum disorder (ASD) patients. Oxytocin disruption has been hypothesized to account for features of ASD, including impaired communication and social behavior, based on animal studies. Recent human studies have shown administration of oxytocin improving emotion recognition, promoting social behavior, and improving auditory processing of social stimuli in ASD patients. In addition to its role in oxytocin signaling, CD38 is involved in the regulation of calcium concentration in airway smooth muscle with impairment of CD38 being implicated in airway diseases like asthma. While a number of studies have implicated rare chromosomal deletions and duplications in helping determine genetic risk for autism, there are to our knowledge no reports describing rearrangements involving CD38 or deletions in patients with ASD. Here, we present two sisters diagnosed with autism and with features of regression—previously acquired speech lost in the second year of life. The younger sister, who also had asthma, inherited a maternal deletion of 4p15.32 that results in a BST1-CD38 fusion transcript. Their mother's deletion was mosaic and she was not affected. Although further work is required to assess functional consequences of the fusion transcript, we hypothesize that the proband's deletion may have served as a risk factor for autism that, when combined with other susceptibility variants, resulted in a more severe presentation than her sister.

Chromosomal abnormalities, such as unbalanced translocations and copy number variants (CNVs), are found in autism spectrum disorders (ASDs) [Sanders et al., 2011]. Many chromosomal abnormalities, including submicroscopic genomic deletions and duplications, are missed by G-banded karyotyping or Fragile X screening alone and are picked up by chromosomal microarrays [Shen et al., 2010]. Translocations involving chromosomes 4 and 8 are possibly the second most frequent translocation in humans and are often undetected in routine cytogenetics [Giglio et al., 2002]. Deletions of 4p16 have been associated with Wolf-Hirschhorn syndrome while 4p16 duplications have been associated with an overgrowth syndrome and mild to moderate mental retardation [Partington et al., 1997]. The 8p23.3 region contains the autism candidate gene DLGAP2, which can contribute to autism when disrupted [Marshall et al., 2008]. There has been a case report of a family with autism spectrum disorder (ASD), prominent obsessional behavior, and overgrowth in patients with der (8) t (4;8) p (16;23) [Partington et al., 1997]. This is an independent report of a male patient with autism, obsessive compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and an overgrowth syndrome, whose de novo unbalanced translocation der (8) t (4;8) p (16.1→ter ; 23.1→ter) was initially missed by routine cytogenetics but detected with SNP microarray, allowing higher resolution of translocation breakpoints.