Deletion 17q12 Is a Recurrent Copy Number Variant that Confers High Risk of Autism and Schizophrenia

Autism spectrum disorders (ASD) and schizophrenia are neurodevelopmental disorders for which recent evidence indicates an important etiologic role for rare copy number variants (CNVs) and suggests common genetic mechanisms. We performed cytogenomic array analysis in a discovery sample of patients with neurodevelopmental disorders referred for clinical testing. We detected a recurrent 1.4 Mb deletion at 17q12, which harbors HNF1B, the gene responsible for renal cysts and diabetes syndrome (RCAD), in 18/15,749 patients, including several with ASD, but 0/4,519 controls. We identified additional shared phenotypic features among nine patients available for clinical assessment, including macrocephaly, characteristic facial features, renal anomalies, and neurocognitive impairments. In a large follow-up sample, the same deletion was identified in 2/1,182 ASD/neurocognitive impairment and in 4/6,340 schizophrenia patients, but in 0/47,929 controls (corrected p = 7.37 × 10−5). These data demonstrate that deletion 17q12 is a recurrent, pathogenic CNV that confers a very high risk for ASD and schizophrenia and show that one or more of the 15 genes in the deleted interval is dosage sensitive and essential for normal brain development and function. In addition, the phenotypic features of patients with this CNV are consistent with a contiguous gene syndrome that extends beyond RCAD, which is caused by HNF1B mutations only

Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women1234

Background: Soy isoflavones are naturally occurring phytochemicals with weak estrogenic cellular effects. Despite numerous clinical trials of short-term isoflavone supplementation, there is a paucity of data regarding longer-term outcomes and safety

Adipocytes Under Environmental Assault: Targets for Obesity?

Abstract In the recent years, there has been a tremendous concern over the possible health threat posed by endocrine-disrupting chemicals (EDCs). These are mostly synthetic chemicals found in various materials such as organo-chlorinated pesticides, industrial chemicals, plastics and plasticizers, fuels, heavy metals, additives or contaminants in food, and personal care products. These chemicals are present in the environment and are with widespread use. Human exposure to EDCs occurs via ingestion of food, dust and water, via inhalation of gases and particles in the air, and through the skin. Data from several animal models, human clinical observations, and epidemiological studies converge to implicate their association with altered reproductive function in males and females, increased incidence of breast cancer, abnormal growth patterns and neuro-developmental delays in children, disruption of adipocyte function, as well as changes in immune function. The EDCs exert their insulting effects by interfering with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, anti-androgenic, thyroid, peroxisome proliferator-activated receptor c, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans. Emerging data from in vitro as well as in vivo models suggest new targets (i.e. adipocyte differentiation and mechanisms involved in weight homeostasis) of abnormal programming by EDCs, and provide strong evidence to support the scientific term ‘obesogen’. The emerging idea of a link between EDCs and obesity expands the focus on obesity from intervention and treatment to include prevention and avoidance of these chemical modifiers. Because expansion of the adipocyte pool is critical for safely storing excess lipid, an understanding how these signaling axes can be altered by EDCs is critical in appreciating how environmental contaminants might contribute to the development of metabolic diseases