👤 Gerald Egger

Swiss adolescents fall short of the WHO's guideline of 60 min of moderate-to-vigorous physical activity (MVPA) per day. Developing targeted interventions or policies requires an understanding of adolescents' daily activity patterns. Since adolescents spend much time at school, it is essential to consider not only leisure but also school segments when assessing physical activity (PA). Therefore, this study investigates how Swiss adolescents' PA is distributed across different school time segments and examines to what extent they meet recommended activity levels. This cross-sectional study uses baseline data from the Active School project. The sample included 666 7th-grade students (mean age = 13.27 ± 0.55 years, 47.7% boys, 51.8% girls, 0.5% diverse) from 12 secondary schools. PA data, gathered over five schooldays using wrist-worn GENEActiv accelerometers, were segmented into physical education (PE), recess, classroom time, entire school time, and leisure time. Activity levels were categorized into inactivity (IN), light physical activity (LPA), and MVPA. Descriptive and inferential statistics (ANOVAs, Within school time, MVPA varied significantly by segment (PE: 30.59%, recess: 18.80%, classroom: 5.69%, Substantial opportunities for PA are lost across all school segments in the Swiss context, with girls consistently less active than boys. Based on these findings, segment-specific and gender-sensitive school PA policies are discussed, and a comprehensive school approach to PA promotion is recommended to support more effective and equitable PA promotion among adolescents. German Clinical Trials Register (DRKS00033362). Date of registration: January 25, 2024. Retrospectively registered. Show less

Autism or autism spectrum disorder (ASD) is a range of neurodevelopmental disorders starting in early childhood and is characterized by impairments in communication and reciprocal social interaction and presence of restricted and repetitive patterns of behavior. The contribution of genetic factors to autism is clear in twin and family studies. It is apparent that, overall, ASD is a complex non-Mendelian disorder. Recent studies suggest that copy number variations (CNVs) play a significant role in the etiology of ASD. For the current work, we recruited 245 family members from 73 ASD families from Styria, Austria. The DNA from probands was genotyped with Affymetrix single nucleotide polymorphism (SNP) 6.0 microarrays to screen for CNVs in their genomes. Analysis of the microarray data was performed using three different algorithms, and a list of stringent calls was compared to existing CNV data from over 2,357 controls of European ancestry. For stringent calls not present in controls, quantitative real-time PCR (qRT-PCR) was used to validate the CNVs in the probands and in their family members. Twenty-two CNVs were validated from this set (five of which are apparently de novo), many of which appear likely to disrupt genes that may be considered as good candidates for neuropsychiatric disorders, including DLG2, S100B, ARX, DIP2A, HPCAL1, and GPHN. Several others disrupt genes that have previously been implicated in autism, such as BDNF, AUTS2, DPP6, and C18orf22, and our data add to the growing evidence of their involvement in ASD. Show less

The GPHN gene codes for gephyrin, a key scaffolding protein in the neuronal postsynaptic membrane, responsible for the clustering and localization of glycine and GABA receptors at inhibitory synapses. Gephyrin has well-established functional links with several synaptic proteins that have been implicated in genetic risk for neurodevelopmental disorders such as autism spectrum disorder (ASD), schizophrenia and epilepsy including the neuroligins (NLGN2, NLGN4), the neurexins (NRXN1, NRXN2, NRXN3) and collybistin (ARHGEF9). Moreover, temporal lobe epilepsy has been linked to abnormally spliced GPHN mRNA lacking exons encoding the G-domain of the gephyrin protein, potentially arising due to cellular stress associated with epileptogenesis such as temperature and alkalosis. Here, we present clinical and genomic characterization of six unrelated subjects, with a range of neurodevelopmental diagnoses including ASD, schizophrenia or seizures, who possess rare de novo or inherited hemizygous microdeletions overlapping exons of GPHN at chromosome 14q23.3. The region of common overlap across the deletions encompasses exons 3-5, corresponding to the G-domain of the gephyrin protein. These findings, together with previous reports of homozygous GPHN mutations in connection with autosomal recessive molybdenum cofactor deficiency, will aid in clinical genetic interpretation of the GPHN mutation spectrum. Our data also add to the accumulating evidence implicating neuronal synaptic gene products as key molecular factors underlying the etiologies of a diverse range of neurodevelopmental conditions. Show less