Fraternal Twins With Autism, Severe Cognitive Deficit, and Epilepsy: Diagnostic Role of Chromosomal Microarray Analysis

We report 2 siblings with biallelic deletions, both of which affect the promoter region and exons 1-5 in the α-NRXN1 isoform, which has a role in the Ca2+-dependent release of neurotransmitters in the central nervous system. Our cases expand the phenotype of biallelic α NRXN 1 mutations and emphasize the important role of NRXN1 in autism and intellectual disability. Chromosomal microarray analysis should be the clinical standard in all specialties for first-tier genetic testing in autistic spectrum disorders.
Source: Seminars in Pediatric Neurology - Category: Neurology Authors: Source Type: research

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AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, intellectual disability, and benign tumors of the brain, heart, skin, and kidney. Animal models have contributed to our understanding of normal and abnormal human brain development, but the construction of models that accurately recapitulate a human pathology remains challenging. Recent advances in stem cell biology with the derivation of human-induced pluripotent stem cells (hiPSCs) from somatic cells from patients have opened new avenues to the study of TSC. This approach combined with gene-editing tools such as CRISPR/C...
Source: Molecular Autism - Category: Molecular Biology Source Type: research
ConclusionsThis study confirms that individuals with PMS are at risk of developing severe neuropsychiatric illness in adolescence or early adulthood, including bipolar disorder, catatonia, and lasting regression of skills. These findings should increase the awareness of these phenotypes and lead to earlier diagnosis and the implementation of appropriate interventions. Our findings also highlight the importance of genetic testing in the work-up of individuals with intellectual disability and acute psychiatric illness or regression. Future research is needed to clarify the prevalence and nature of psychiatric disorders and r...
Source: Journal of Neurodevelopmental Disorders - Category: Neurology Source Type: research
We report two independent subjects with 16q12.1q21 deletion syndrome presenting with dysmorphic facial features, developmental delay, strabismus, and aggressive behavior. A minimal region of overlap spanning 1.7 Mb on chromosome 16, including IRX5, GNAO1, and NUDT21 genes was shared among these two cases and those previously reported. This minimal region of overlap suggests the potential pathogenic role of these genes, previously implicated in diseases of the central nervous system. PMID: 32045705 [PubMed - as supplied by publisher]
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research
This study uncovers a critical role of KAT8 in cerebral and NSPC development, identifies 9 individuals with KAT8 variants, and links deficient H4K16 acylation directly to intellectual disability, epilepsy, and other developmental anomalies.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
ConclusionThis report, along with other recent observations, suggests the hypothesis that the BP region comprised between BP3 and BP5 in chromosome 15q13 is involved in several brain human dysfunctions, including impairment of the language development and, its deletion, may be directly or indirectly responsible for the speech delay and language deficit in the affected individuals.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
ConclusionsOur results indicate the prevalence of multiple comorbidities varies across the lifespan in DS, and in adults, rates for psychiatric comorbidities show different patterns for males and females relative to expected population rates. Further, most health comorbidities are not associated with poorer cognitive outcomes in DS, apart from autism and epilepsy. It is essential for clinicians to consider such differences to provide appropriate care and treatment for those with DS and to provide prognostic information relating to cognitive outcomes in those with comorbidities.
Source: Journal of Neurodevelopmental Disorders - Category: Neurology Source Type: research
Abstract Mutations in the X-linked gene IQSEC2 are associated with multiple cases of epilepsy, epileptic encephalopathy, intellectual disability and autism spectrum disorder, the mechanistic understanding and successful treatment of which remain a significant challenge in IQSEC2 and related neurodevelopmental genetic diseases. To investigate disease etiology, we studied behaviors and synaptic function in IQSEC2 deficient mice. Hemizygous Iqsec2 null males exhibit growth deficits, hyperambulation and hyperanxiety phenotypes. Adult hemizygotes experience lethal spontaneous seizures, but paradoxically have a signific...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
In conclusion, school-aged children with CP very often screened positive for ASD and/or ADHD. The prevalence of ASD and ADHD is most likely underestimated in children with CP. These screening findings require further investigations.
Source: European Child and Adolescent Psychiatry - Category: Psychiatry Source Type: research
ConclusionMEK-ERK and MNK-eIF4E pathways regulate protein translation, and our results suggest that aberrant translation distinct in TSC1/2-deficient NPCs could play a role in neurodevelopmental defects. Our data showing upregulation of these signaling pathways by rapamycin support a strategy to combine a MEK or a MNK inhibitor with rapamycin that may be superior for TSC-associated CNS defects. Importantly, our generation of isogenic sets of NPCs from TSC patients provides a valuable platform for translatome and large-scale drug screening studies. Overall, our studies further support the notion that early developmental eve...
Source: Molecular Autism - Category: Molecular Biology Source Type: research
CONCLUSION: Intellectually disabled persons can be treated in a multimodal, multiprofessional approach. As of early 2019, there were 38 medical centers for adults with intellectual disability or severe multiple disabilities in Germany (Medizinische Behandlungszentren für Erwachsene mit geistiger Behinderung oder schweren Mehrfachbehinderungen, MZEB), where they can be cared for with due attention to their special needs. PMID: 31888794 [PubMed - in process]
Source: Deutsches Arzteblatt International - Category: General Medicine Tags: Dtsch Arztebl Int Source Type: research
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