Clinical correlates in children with autism spectrum disorder and CNVs: systematic investigation in a clinical setting.
This study documents the importance of measuring the physical and neurobehavioural correlates of ASD phenotypes to unravel the underlying molecular mechanisms in patient subgroups. PMID: 32159884 [PubMed - as supplied by publisher]
PCDH19 (protocadherin-19) was first identified as a cause of epilepsy and intellectual disability in 2008 . Pathogenic variants in PCDH19 are associated with a complex neurodevelopmental syndrome characterized by epilepsy with fever-related clusters, intellectual disability, autism spectrum disorder and behavioral comorbidity . The phenotypic spectrum related to PCDH19 is broadening to include patients with milder phenotype .
Mutations in SLC6A1, encoding γ-aminobutyric acid (GABA) transporter 1 (GAT-1), have been recently associated with a spectrum of epilepsy syndromes, intellectual disability and autism in clinic. However, the path...
Mutations in PACS2 gene are responsible for an early-onset developmental and epileptic encephalopathy, presenting with seizures starting within the first weeks of life. The phenotype of this new syndrome is also characterized by hypotonia, global developmental delay, intellectual disability with or without autistic features, mild facial dysmorphism and cerebellar dysgenesis with folia abnormalities. [1,2] PACS2 gene encodes for a multifunctional sorting protein highly expressed in cervical spinal cord and cerebellum and involved in mediating secretory pathway traffic and formation of contacts between endoplasmic reticulum ...
This article will summarise the current state of knowledge linking mutations in presynaptic genes to ne urodevelopmental disorders by sequentially covering the various stages of the synaptic vesicle life cycle. It will also discuss how perturbations of specific stages within this recycling process could translate into human disease. Finally, it will also provide perspectives on the potential for futur e therapy that are targeted to presynaptic function.
ConclusionsOur results indicate thatTsc1 haploinsufficiency in MGE-derived inhibitory cells upregulates mTORC1 activity in these interneurons, reduces their synaptic inhibition of pyramidal cells, and alters contextual fear discrimination and spatial working memory. Thus, selective dysregulation of mTORC1 function in Nkx2.1-expressing inhibitory cells appears sufficient to impair synaptic inhibition and contributes to cognitive deficits in theTsc1 mouse model of TSC.
CONCLUSION: It should be routine to screen for cognitive and behavioral difficulties for all patients with DS. There is a need for more robust studies regarding intellectual and behavioral disorders in patients with DS. These should be large population-based or multinational studies that employ standardized instruments. PMID: 32334365 [PubMed - as supplied by publisher]
ConclusionsOur results indicated that patients with the samePCDH19 mutation in a family may show intrafamilial phenotypic variability. Givening the mother of the proband was 18 weeks pregnant and intends to have a prenatal diagnosis, the more reasonable and less harmful strategies for prenatal diagnosis could be chosen based on the results of noninvasive prenatal testing and genetic testing.
In this study, adults with ASD had a unique social profile with different clinical needs compared to adults with only ID or to adults with co ‐occurring ASD and ID. Adults with only ID and those with co‐occurring ASD shared many of the same social characteristics and high clinical needs. The analysis of these profiles will be useful in developing services that better meet the needs of this complex group.
Epilepsy and autism frequently co-occur. Epilepsy confers an increased risk of autism and autism confers an increased risk of epilepsy. Specific epilepsy syndromes, intellectual disability, and female gender present a particular risk of autism in individuals with epilepsy. Epilepsy and autism are likely to share common etiologies, which predispose individuals to either or both conditions. Genetic factors, metabolic disorders, mitochondrial disorders, and immune dysfunction all can be implicated.
Pre-eclampsia was associated with a slightly increased risk of epilepsy, autism and other neurodevelopmental problems in offspring.