BackgroundCopy number variations (CNVs) have been implicated in psychiatric and neurodevelopmental disorders. Especially, 15q13.3 deletions are strongly associated with autism spectrum disorder (ASD), intellectual disability (ID), schizophrenia (SCZ), attention deficithyperactivity disorder (ADHD), and mood disorder.Case PresentationWe present two siblings with ASD. They had a father with bipolar disorder (BD). Patient 1 is a 21‐year‐old female with ASD and mild ID, who had language delay and repetitive behavior in childhood, social difficulties, and refused to go to school because of bullying. She was hospitalized in a psychiatric hospital several times. Patient 2 is a 19‐year‐old male with ASD and ADHD. He did not have developmental delay, but had social difficulties and impulsiveness, then refused to go to school because of bullying. He was treated by a psychiatrist for anxiety and disrupted sleep rhythms. Array comparative genomic hybridization was performed for the siblings and parents. 15q13.3 deletions were detected in the siblings and their healthy mothers. No other pathogenic CNVs were detected. We performed whole‐genome sequencing of the family and identified 13 rare missense variants in brain‐expressed genes, which may be responsible for the phenotypic differences between the siblings and their mother.ConclusionsThis study shows incomplete penetrance and variable expressivity in 15q13.3 deletions. We detected second‐hit variants that may explain the phenotypic differences within this family. In addition, detecting 15q13.3 deletions may lead to early diagnosis and a better prognosis with careful follow‐up.
Accumulating epidemiological studies have suggested a positive association between advanced paternal age at conception and the increased risk of neurodevelopmental outcomes such as autism spectrum disorder (ASD) in their children. Recent biological studies using human sperm have identified increased de novo mutations in aged fathers, and hyper‐ or hypomethylation has been identified in the sperm from aged rodents. Dysregulation of DNA methylation in sperm may explain the transgenerational effects on the pathogenesis of ASD. However, compared to these epigenetic changes in the sperm of aged males, the effects of inherited predisposition from germ cells are largely unknown. Here, we use single‐cell transcriptome data sets from 13 cell lines, including 12 ASD‐associated CNVs models and control, that are performed neural differentiation from mouse embryonic stem cells. This study performed comprehensive bioinformatic analyses such as gene ontology (GO), network, pathway, and upstream regulator analyses. Through these analyses, we identify several susceptible pathways, such as chromatin and ubiquitin, in addition to translational and oxidative phosphorylation. Our results suggest that dysregulation of epigenetic chromosome remodeling and ubiquitin‐proteasome pathway in the germ cell is a possible modulator for subsequent differentiated cells, sperm, and egg, as a risk factor for the neurodevelopmental disorder.
Background People with intellectual disabilities (IDs) and their caregivers face difficulties during the COVID-19 pandemic. However, limited studies have comprehensively investigated their challenges, especially in Japan. We aimed to clarify the concerns and needs of people with IDs and their caregivers during the COVID-19 pandemic in Japan. Method From March to August 2021, 27 in-depth interviews were conducted with principal caregivers of people with moderate to profound IDs in Japan. We then transcribed the interviews and conducted deductive coding using predetermined codes focused on their daily life difficulties. Inductive coding was used to ensure that no important themes were overlooked. Results We found four concerns and four needs among people with IDs and their caregivers as significant themes. Conclusions Our results provide useful information for supporting people with IDs and their caregivers, especially among those who need medical or social care in accordance with the infection control and social-distancing policies.
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