Identification of DNA methylation episignature for the intellectual developmental disorder, autosomal dominant 21 syndrome, caused by variants in the CTCF gene.

PURPOSE: The main objective of this study was to assess clinical features and genome-wide DNA methylation profiles in individuals affected by intellectual developmental disorder, autosomal dominant 21 (IDD21) syndrome, caused by variants in the CCCTC-binding factor (CTCF) gene. METHODS: DNA samples were extracted from peripheral blood of 16 individuals with clinical features and genetic findings consistent with IDD21. DNA methylation analysis was performed using the Illumina Infinium Methylation EPIC Bead Chip microarrays. The methylation levels were fitted in a multivariate linear regression model to identify the differentially methylated probes. A binary support vector machine classification model was constructed to differentiate IDD21 samples from controls. RESULTS: We identified a highly specific, reproducible, and sensitive episignature associated with CTCF variants. Six variants of uncertain significance were tested, of which 2 mapped to the IDD21 episignature and clustered alongside IDD21 cases in both heatmap and multidimensional scaling plots. Comparison of the genomic DNA methylation profile of IDD21 with that of 56 other neurodevelopmental disorders provided insights into the underlying molecular pathophysiology of this disorder. CONCLUSION: The robust and specific CTCF/IDD21 episignature expands the growing list of neurodevelopmental disorders with distinct DNA methylation profiles, which can be applied as supporting evidence in variant classification.

Demographic, Clinical and Biochemical Characteristics of Pediatric Obesity: Interim Analysis of a Larger Prospective Study.

INTRODUCTION: Pediatric obesity is a common nutritional disorder that affects more than a third of the young population and predis-poses individuals to greater future morbidity and mortality. Materials and methods: Sixty-two children were recruited in the study. Demographic and clinical information regarding the pa-tients and their parents was collected. Data about the weight, height, systolic (SP) and diastolic (DP) blood pressure, lipid metabolic profile, thyroid hormone levels, glucose and insulin levels before and after oral glucose tolerance test (OGTT) of participants were also collected. Body mass index (BMI) was calculated and patients were classified into groups according to the International Obesity Task Force criteria. Descriptive, comparative parametric, non-parametric tests and Spearman's ranked correlations were used in the statistical analysis. Results: The study sample consisted of 34 males and 28 females aged 11.6 and 11.8 years, respectively (p=0.781). The mean BMI was 30.5 (SD 5.5): 8 of participant had normal weight (≤25 BMI), 22 were overweight (25-30 BMI), and 32 were obese (≥30 BMI). The chil-dren's BMIs were significantly associated with parental BMIs (r=0.395, p=0.004). Both SP and DP were significantly different between BMI subgroups (p=0.005 and p=0.001, respectively) with the obese group having the highest values (post-hoc Benjamini,  p=0.004). Obese children had lower average T4 levels when compared to the comparators (7.5 µg/dL vs. 9.9 µg/dL, p=0.021). Obese children had significantly lower baseline glucose levels and higher insulin levels when compared to the overweight/normal BMI children (73.8 mg/dL vs. 86.4 mg/dL, p.

Correlation of serum adiponectin and leptin concentrations with anthropometric parameters in newborns.

INTRODUCTION: It has been shown that some adipocytokines and their mutual relationship can be indicators of fetal and neonatal growth. Physiological role of leptin and adiponectin in fetal and neonatal growth is not well established. OBJECTIVES: The aim of this study was to assess the correlation of the anthropometrics parameters and serum concentration of leptin and adiponectin levels in healthy newborns. METHODS: A cohort of 110 neonates, born after uncomplicated singleton pregnancies at term, were classified as AGA (n = 60), SGA (n = 30) and LGA (n = 20) according to the Lubchenco curves. Anthropometric parameters of the neonates: birth weight (BW), birth length (BL), body weight/body length ratio (BW/ BL), Body Mass Index (BMI) and Ponderal Index (II) were recorded after birth. RESULTS: Mean serum leptin and adiponectin levels in both sexes were not significantly different (male: 1.8 +/- 0.75; 29.5 +/- 22.89 and female: 2.0 +/- 0.99; 31.6 +/- 23.51 ng/mL). There was a significant difference between leptin levels in AGA and LGA newborns 11.9 +/- 0.84 vs. 3.1 +/- 1.50 ng/mL) (p < 0.05), and in adiponectin levels between AGA and LGA compared to SGA newborns (32. +/- 23.29 and 43.4 +/- 31.24 vs. 12.6 +/- 2.43 ng/mL, respectively; p < 0.05; p < 0.05). Leptin and adiponectin levels were positively correlated with BW (r = 0.63 and r = 0.41), BL (r = 0.63, r = 0.42), BW/BL (r = 0.61, r = 0.41), BMI (r = 0.54, r = 0.35), and PI (r = 0.47, r = 0.29, (p < 0.01). CONCLUSION: Significantly higher adiponectin levels were found in AGA neonates compared to SGA neonates. Leptin and adiponectine levels were positively correlated with birth weight. These findings suggest that these adipocytokines may be involved in fetal growth regulation.