ABSTRACT
Variants in the chromodomain helicase DNA-binding protein 8 (CHD8) have been associated with intellectual disability (ID), autism spectrum disorders (ASDs) and overgrowth and CHD8 is one of the causative genes for OGID (overgrowth and ID). We investigated 25 individuals with CHD8 protein truncating variants (PTVs), including 10 previously unreported patients and found a male to female ratio of 2.7:1 (19:7) and a pattern of common features: macrocephaly (62.5%), tall stature (47%), developmental delay and/or intellectual disability (81%), ASDs (84%), sleep difficulties (50%), gastrointestinal problems (40%), and distinct facial features. Most of the individuals in this cohort had moderate-to-severe ID, some had regression of speech (37%), seizures (27%) and hypotonia (27%) and two individuals were non-ambulant. Our study shows that haploinsufficiency of CHD8 is associated with a distinctive OGID syndrome with pronounced autistic traits and supports a sex-dependent penetrance of CHD8 PTVs in humans.
Subject(s)
DNA-Binding Proteins/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Genetic Variation , Phenotype , Transcription Factors/genetics , Adolescent , Alleles , Amino Acid Substitution , Child , Child, Preschool , Facies , Female , Genetic Association Studies/methods , Genotype , Humans , Male , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/geneticsABSTRACT
The COVID-19 pandemic is revealing growing reports of atypical presentation of the disease beyond the respiratory system. SARS-CoV-2 infection has been linked to multisystem vasculopathy including cardiopulmonary, cerebral and renal vasculature, potentially brought on by a dysregulated host immune response in a probable setting of a cytokine storm. Here, we describe a case of a previously healthy and active 74-year-old man presenting with acute cognitive decline with preceding non-specific influenza-like symptoms. He was then diagnosed with cerebral amyloid angiopathy (CAA)-associated intracerebral haemorrhage and was found to be COVID-19 positive. COVID-19-induced immune response may have further compromised the cerebral vessels already weakened by CAA, triggering multiple microhaemorrhages leading to clinical presentation. The limited evidence about the heterogeneity of COVID-19 manifestations suggests that clinicians should be aware and screen for concurrent COVID-19 in patients presenting with neurological features during the peak of this pandemic, as this offers the best chance for better clinical outcome.
Subject(s)
COVID-19 , Pandemics , Aged , Brain/diagnostic imaging , Cerebral Hemorrhage , Humans , Male , SARS-CoV-2ABSTRACT
This study examined the effect of idle time setting on the estimation of computer use times by electronic activity monitoring and validated its use by comparing it with video record observations. Twenty-four study subjects were recruited and their work with computers was monitored for 1 h. With the estimates by video record observation as references, the best idle time settings for electronic activity monitoring with the least relative errors were 25, 2.5 and 2.5 s, respectively, for total computer, keyboard and mouse use time estimations. These estimates were highly correlated with the corresponding references (r = 0.918-0.964, p < 0.0001), accompanied by limited mean estimate differences ranging from -3.0 +/- 2.8% to 1.3 +/- 1.6%. The estimates by self-report were moderately correlated with the corresponding references (r = 0.387-0.678), with greater mean estimate differences. This study concluded that, for electronic activity monitoring methods, the most appropriate thresholds for idle time setting are 25 s, 2.5 s and 2.5 s for total computer, keyboard and mouse use time estimates, respectively. This method may help evaluate physical work-loading with computer works through a large-scale epidemiological study.