Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations in the VPS33B and VIPAS39. Here, we report novel mutations identified in four patients with ARC syndrome. We analyzed the entire coding regions of the VPS33B and VIPAS39 genes by direct sequencing. To detect novel splice site mutations, mRNA transcripts were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. All four patients had compound heterozygous variants in the VPS33B gene. One patient had a previously reported splice site variant with unknown significance, c.239+5G>A, and a novel nonsense mutation, c.621G>A. The other three patients had the c.403+2T>A mutation, and each of them carried one of the splice site variants, c.239+5G>A or c.499-11G>A. c.239+5G>A and c.499-11G>A created novel splice sites which resulted in abnormal transcripts. No significant VIPAS39 mutation was detected in all patients. In patients suspected with ARC syndrome, mutation analysis of the VPS33B gene should be employed as a primary diagnostic test before performing invasive testing procedures such as organ biopsies. Performing mRNA analysis can be useful in predicting the pathogenic phenotype when the mutation seems to affect a normal splicing mechanism.

Childhood obesity has increased worldwide, and many clinical and public interventions have attempted to reduce morbidity. We aimed to determine the metabolomic signatures associated with weight control interventions in children with obesity. Forty children from the “Intervention for Children and Adolescent Obesity via Activity and Nutrition (ICAAN)” cohort were selected according to intervention responses. Based on changes in body mass index z-scores, 20 were responders and the remaining non-responders. Their serum metabolites were quantitatively analyzed using capillary electrophoresis time-of-flight mass spectrometry at baseline and after 6 and 18 months of intervention. After 18 months of intervention, the metabolite cluster changes in the responders and non-responders showed a difference on the heatmap, but significant metabolites were not clear. However, regardless of the responses, 13 and 49 metabolites were significant in the group of children with obesity intervention at 6 months and 18 months post-intervention compared to baseline. In addition, the top five metabolic pathways (D-glutamine and D-glutamate metabolism; arginine biosynthesis; alanine, aspartate, and glutamate metabolism; TCA cycle; valine, leucine, and isoleucine biosynthesis) including several amino acids in the metabolites of obese children after 18 months were significantly changed. Our study showed significantly different metabolomic profiles based on time post obesity-related intervention. Through this study, we can better understand and predict childhood obesity through metabolite analysis and monitoring.

Steroid 21-hydroxylase deficiency is caused by inactivating mutations in the CYP21A2 gene. This paper reports on the mutation spectrum and the genotype-phenotype correlation of 21-hydroxylase deficiency. 72 unrelated patients with congenital adrenal hyperplasia (CAH) were included. Molecular analysis of CYP21A2 was performed, via the multiplex ligation-dependent probe amplification (MLPA) analysis and sequence-specific differenzial PCR amplification of the CYP21A2 and CYP21A1P genes, using 4 pair-wise sequence-specific primers, followed by sequencing of the entire CYP21A2 gene. Large gene deletions were identified in 45 (31.3%) of the 144 unrelated CAH alleles, whereas the most frequent point mutations were intron 2 splice mutations (c.293-13A>G) (41/144, 28.5%). The MLPA analysis successfully identified 23 of 72 patients (31.9%) with single copy deletion in CYP21A2. This paper describes a rapid and accurate method for the molecular diagnosis of 21-hydroxylase deficiency, which relies on the identification of point mutations and structural rearrangements within the CYP21A2 gene.

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Context.—Helicobacter pylori infection is primarily acquired during childhood and persists throughout life in the absence of eradication with antibiotics. Helicobacter pylori infection induces methylation in the promoter CpG island loci in gastric epithelial cells. Thus, aberrant CpG island hypermethylation in gastric epithelial cells likely occurs early in life, although there are no existing data supporting this notion. Objectives.—To identify whether aberrant CpG island hypermethylation occurs in pediatric stomach mucosa in association with H pylori infection and to compare methylation profiles of samples from pediatric and adult stomach tissues. Design.—We analyzed pediatric (n  =  47) and adult (n  =  38) gastric mucosa samples for their methylation status in 12 promoter CpG island loci using the MethyLight assay and compared the number of methylated genes and the methylation levels in individual genes between H pylori–positive and H pylori–negative sample results and between pediatric and adult samples. Results.—The average number of methylated genes was significantly higher in H pylori–infected pediatric samples than in H pylori–negative pediatric samples (3.4 versus 0.3, P < .001) and in H pylori–infected adult samples than in H pylori–negative adult samples (7.6 versus 0.9, P < .001). Seven genes showed significantly higher methylation levels in H pylori–infected pediatric samples than in H pylori–negative pediatric samples (all values were P < .05). Conclusions.—These results indicate that CpG island hypermethylation occurs in pediatric gastric mucosa in association with H pylori infection and that the genes affected by H pylori–associated hypermethylation were similar in pediatric and adult samples.