More Clinical Overlap between 22q11.2 Deletion Syndrome and CHARGE Syndrome than Often Anticipated.

CHARGE (coloboma, heart defects, atresia of choanae, retardation of growth and development, genital hypoplasia, and ear abnormalities) and 22q11.2 deletion syndromes are variable, congenital malformation syndromes that show considerable phenotypic overlap. We further explored this clinical overlap and proposed recommendations for the genetic diagnosis of both syndromes. We described 2 patients clinically diagnosed with CHARGE syndrome, who were found to carry a 22q11.2 deletion, and searched the literature for more cases. In addition, we screened our cohort of CHD7 mutation carriers (n = 802) for typical 22q11.2 deletion features and studied CHD7 in 20 patients with phenotypically 22q11.2 deletion syndrome but without haploinsufficiency of TBX1. In total, we identified 5 patients with a clinical diagnosis of CHARGE syndrome and a proven 22q11.2 deletion. Typical 22q11.2 deletion features were found in 30 patients (30/802, 3.7%) of our CHD7 mutation-positive cohort. We found truncating CHD7 mutations in 5/20 patients with phenotypically 22q11.2 deletion syndrome. Differentiating between CHARGE and 22q11.2 deletion syndromes can be challenging. CHD7 and TBX1 probably share a molecular pathway or have common target genes in affected organs. We strongly recommend performing CHD7 analysis in patients with a 22q11.2 deletion phenotype without TBX1 haploinsufficiency and conversely, performing a genome-wide array in CHARGE syndrome patients without a CHD7 mutation.

Long-term nicotine adaptation in Caenorhabditis elegans involves PKC-dependent changes in nicotinic receptor abundance.

Chronic exposure to nicotine leads to long-term changes in both the abundance and activity of nicotinic acetylcholine receptors, processes thought to contribute to nicotine addiction. We have found that in Caenorhabditis elegans, prolonged nicotine treatment results in a long-lasting decrease in the abundance of nicotinic receptors that control egg-laying. In naive animals, acute exposure to cholinergic agonists led to the efficient stimulation of egg-laying, a response mediated by a nicotinic receptor functionally expressed in the vulval muscle cells. Overnight exposure to nicotine led to a specific and long-lasting change in egg-laying behavior, which rendered the nicotine-adapted animals insensitive to simulation of egg-laying by the nicotinic agonist and was accompanied by a promoter-independent reduction in receptor protein levels. Mutants defective in the gene tpa-1, which encodes a homolog of protein kinase C (PKC), failed to undergo adaptation to nicotine; after chronic nicotine exposure they remained sensitive to cholinergic agonists and retained high levels of receptor protein in the vulval muscles. These results suggest that PKC-dependent signaling pathways may promote nicotine adaptation via regulation of nicotinic receptor synthesis or degradation.

A comparison of three indexes to assess the dimensions of structural analysis of social behavior.

Structural Analysis of Social Behavior (SASB) is an increasingly popular model of interpersonal and intrapsychic interactions that provides a flexible assessment methodology ranging from an observer-based coding system to a modifiable objective self-report questionnaire: the Intrex. Published research using the Intrex has varied in the methods employed to assess the fundamental dimensions of affiliation and autonomy of SASB. In this article, we review the conceptual and computational differences among 3 indexes to assess the SASB dimensions. Empirical comparisons revealed good support for convergent validity but significant differences in distribution characteristics and orthogonality. These results have direct implications for assessment strategies, statistical analyses, and interpretation of both clinical assessments and clinical research. Results are discussed with reference to developing guidelines for assessment and research use of SASB via self-report.