Sotos syndrome associated with Hirschsprung's disease: a new case and exome-sequencing analysis.

BackgroundSotos syndrome (SoS) is an overgrowth disorder with various congenital anomalies and is usually accompanied by other clinical problems. However, anorectal malformations have not been documented as part of the SoS entity. Our objective is to report on a case of SoS associated with Hirschsprung's disease (HSCR) and subsequent genetic analysis.MethodsA 2-year-old boy with SoS experienced constipation since infancy and ultimately showed an aganglionic segment in the histopathologic examination, which was followed by exome-sequencing analysis.ResultsIn the genetic test for SoS diagnosis, two novel mutations of NDS1, c.2465C>A (p.Ser822Tyr) and c.4347T>A (p.Cys1449*), were observed and verified by resequencing in the patient and his parents. In further whole-exome-sequencing analysis using the patient's blood DNA, which was followed by a comparison analysis with the results of our previously reported genome-wide association study (GWAS) of HSCR, three genes (ZNF827, FGD2, and KCNJ12) with significance for HSCR from our previous GWAS were overlapped among the genes showing variants in the exome sequencing.ConclusionThis is the first reported patient with SoS and HSCR. Further studies are required to determine whether there is a genetic relationship between SoS and HSCR.

Reliability and validity of Korean version of modified: Yale preoperative anxiety scale.

PURPOSE: The modified Yale Preoperative Anxiety Scale (mYPAS) was developed for evaluating the level of preoperative anxiety in children. The purpose of this study was to develop a Korean version of the mYPAS (K-mYPAS) and to establish its validity and reliability based on the Korean preoperative pediatric patients. METHODS: K-mYPAS was made through stringent back-translation procedure. Total enrolled 102 patients answered questionnaires of Korean version of State-Trait Anxiety Inventory for Children (K-STAIC), and were videotaped for 2 to 5 minutes before induction of anesthesia. Three observers of experienced psychiatrist, surgeon, and nurse analyzed videotape with K-mYPAS comparing to K-STAIC. The inter- and intraobservers reliability, concurrent and construct validity, sensitivity, specificity, and predictive value were analyzed. RESULTS: The value of Cronbach α for interobservers reliability was 0.939 and intraobserver reliability was statistically significant (P < 0.001). Concurrent and construct validity were also statistically significant (P < 0.001 and P < 0.001, respectively). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 81.3%, 91.4%, 81.3%, 91.4%, and 88.2%, respectively. CONCLUSION: The K-mYPAS had good psychometric properties and can be used as a reliable and valid instrument for the assessment of preoperative anxiety in children.

Gene expression profile of necrotizing enterocolitis model in neonatal mice.

BACKGROUND: Necrotizing enterocolitis (NEC) characterized by intestinal necrosis is one of the most common gastrointestinal emergencies in newborns. The main purpose of this study was to evaluate the whole genome expression levels in a NEC mouse model controlled with breast milk. METHODS: This study induced a NEC model in mice of gestational ages of 18-21 days by intensive hypoxic insult and permitted breast-feeding instead of formula feeding. After evaluating the NEC status in the small intestines of neonatal mice by histological examination, a genome-wide gene expression profile study was completed using microarray analysis. RESULTS: A total of 72 genes (38 down-regulated and 34 up-regulated) were observed to have significantly different expression profiles in the NEC mouse model compared with the normal control animals, based on a significance at fold change ≥ 2 and P < 0.05. In particular, down-regulated Hist1h2aa and up-regulated Ube2i showed the most significant signals (P = 0.0008 for both genes). In an additional gene ontology analysis, the endopeptidase related categories (specifically, serine-type endopeptidase inhibitor activity, P = 8.95 × 10(-5); Pcorr = 0.008) appeared to affect NEC development in the mouse model. CONCLUSION: Although replications and functional evaluations are needed, our results suggest that several genes may have different expression profiles in the NEC mouse model. In particular, endopeptidase related genes (which are also known to be relevant to NEC), as identified through gene ontology analysis, may represent attractive targets for future research.