Molecular Cytogenetic Analysis and Resequencing of Contactin Associated Protein-Like 2 in Autism Spectrum Disorders

Autism spectrum disorders (ASD) are a group of related neurodevelopmental syndromes with complex genetic etiology.1 We identified a de novo chromosome 7q inversion disrupting Autism susceptibility candidate 2 (AUTS2) and Contactin Associated Protein-Like 2 (CNTNAP2) in a child with cognitive and social delay. We focused our initial analysis on CNTNAP2 based on our demonstration of disruption of Contactin 4 (CNTN4) in a patient with ASD;2 the recent finding of rare homozygous mutations in CNTNAP2 leading to intractable seizures and autism;3 and in situ and biochemical analyses reported herein that confirm expression in relevant brain regions and demonstrate the presence of CNTNAP2 in the synaptic plasma membrane fraction of rat forebrain lysates. We comprehensively resequenced CNTNAP2 in 635 patients and 942 controls. Among patients, we identified a total of 27 nonsynonymous changes; 13 were rare and unique to patients and 8 of these were predicted to be deleterious by bioinformatic approaches and/or altered residues conserved across all species. One variant at a highly conserved position, I869T, was inherited by four affected children in three unrelated families, but was not found in 4010 control chromosomes (p = 0.014). Overall, this resequencing data demonstrated a modest nonsignificant increase in the burden of rare variants in cases versus controls. Nonethless, when viewed in light of two independent studies published in this issue of AJHG showing a relationship between ASD and common CNTNAP2 alleles,4,5 the cytogenetic and mutation screening data suggest that rare variants may also contribute to the pathophysiology of ASD, but place limits on the magnitude of this contribution

Rapidly progressive glomerulonephritis in a child with Henoch-Schönlein Vasculitis and familial Mediterranean fever

Henoch-Schonlein Vasculitis (HSV) is systemic small vessel vasculitis involving the skin, kidney, joints, and gastrointestinal tract. The proportion of patients reported to have renal involvement varies between 20% and 80%. Rapidly progressive glomerulonephritis (RPGN)is rare syndrome in children, characterized by clinical features of glomerulonephritis (GN) and rapid loss of renal function. We present a severe kidney involvement in a 14 year old boy with HSV in who is carring MEFV mutation. A 14 year old boy had developed sudden onset of palpable purpuric rash on his extensor surfaces of lower extremities. He had elevated an erythrocyte sedimentation rate (ESR) (45 mm/h), C-reactive protein (3.74 mg/dl), serum urea 66 mg/dl, serum creatinine 1.8 mg/dl. Also, he had hypocomplementemia. Antinuclear antibody, anti ds DNA, antineutrophil cytoplasmic antibody, anticardiolipine antibodies were negative. Urinalysis revealed macroscopic hematuria and proteinuria with a 24-h urinary protein excretion of 55 mg/m2/h. The renal biopsy specimen showed crescentic and necrotizing glomerulonephritis. He had also M694V/E148Q compound heterozygote mutation. Clinical symptoms and renal failure resolved with intermittant hemodialysis and medical therapy

Quality of Inclusive Preschool Classrooms: Predictive Variables

Preschool inclusion is an issue that has become more prominent and is frequently targeted in the literature in recent years. Previous studies regarding preschool inclusion were conducted with teachers, typically developing children, and children with disabilities as well as about how the inclusive practices could be more effective and which variables would affect the quality of preschool inclusion. Recently, the concept of ``quality{''} in inclusive preschool becomes one of the current issues in the field. The quality of the inclusion is examined as the process quality, structural quality, and global quality it is influenced by several factors such as experience and education of teachers, teacher/child ratio and knowledge of teachers related to implementation of inclusive practices. The purpose of this study, which utilized correlational screening model, was to reveal the variables which predict the overall quality of inclusive preschool classrooms in Turkey. The data were collected by Teacher Information Form, Student-Teacher Relationship Scale, Opinions Relative to Integration of Students with Disabilities, and Abilities Index in 47 preschool classrooms as well as the third researcher assessed the quality of the classrooms by using Inclusive Classroom Profile. To test the predictive value of all variables, a stepwise regression model was used. Analyses showed that the overall quality of the inclusive preschool classrooms was predicted by the teachers' opinions regarding inclusion, having courses related to preschool inclusion, and teachers' relationships with their students. The results are discussed in the framework of the existent literature and suggestions related to implications and future research are offered

Comparison of the efficacy of once- and twice-daily colchicine dosage in pediatric patients with familial Mediterranean fever - a randomized controlled noninferiority trial

Background: In this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF)

Low levels of urinary epidermal growth factor predict chronic kidney disease progression in children

Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6-17 years with baseline estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m(2). uEGF levels were measured in archived urine collected within 6 months of enrollment. Congenital abnormalities of the kidney and urinary tract were the most common cause of CKD, with glomerular diseases accounting for <10% of cases. Median eGFR at baseline was 28 ml/min/1.73 m(2), and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m(2), or initiation of renal replacement therapy). In a Cox proportional hazards model, higher uEGF/Cr was associated with a decreased risk of CKD progression (HR 0.76; 95% CI 0.69-0.84) independent of age, sex, baseline eGFR, primary kidney disease, proteinuria, and systolic blood pressure. The addition of uEGF/Cr to a model containing these variables resulted in a significant improvement in C-statistics, indicating better prediction of the 1-, 2- and 3-year risk of CKD progression. External validation in a prospective cohort of 222 children with CKD demonstrated comparable results. Thus, uEGF may be a useful biomarker to predict CKD progression in children with CKD