Autism spectrum disorders (ASDs) are common neurodevelopmental disorders with a strong genetic etiology. However, due to the extreme genetic heterogeneity of ASDs, traditional approaches for gene discovery are challenging. Next-generation sequencing technologies offer an opportunity to accelerate the identification of the genetic causes of ASDs. Here, we report the results of whole-exome sequence in a cohort of 20 ASD patients. By extensive bioinformatic analysis, we identified novel mutations in seven genes that are implicated in synaptic function and neurodevelopment. After sequencing an additional 47 ASD samples, we identified three different missense mutations in ANK3 in four unrelated ASD patients, one of which, c.4705T>G (p.S1569A), is a de novo mutation. Given the fact that ANK3 has been shown to strongly associate with schizophrenia and bipolar disorder, our findings support an association between ANK3 mutations and ASD susceptibility and imply a shared molecular pathophysiology between ASDs and other neuropsychiatric disorders.
Physiological roles of axonal ankyrins in survival of premyelinated axons and localization of voltage-gated sodium channels
Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility
Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting
Identification of a novel Cys146X mutation of SOD1 in familial amyotrophic lateral sclerosis by whole-exome sequencing
Homozygous and heterozygous disruptions of ANK3: at the crossroads of neurodevelopmental and psychiatric disorders
Towards a molecular characterization of autism spectrum disorders: an exome sequencing and systems approach
β-III spectrin underpins ankyrin R function in Purkinje cell dendritic trees: protein complex critical for sodium channel activity is impaired by SCA5-associated mutations
The contribution of protein intrinsic disorder to understand the role of genetic variants uncovered by autism spectrum disorders exome studies
Dysplastic spondylolysis is caused by mutations in the diastrophic dysplasia sulfate transporter gene
Psychiatric risk factor ANK3/ankyrin-G nanodomains regulate the structure and function of glutamatergic synapses
Rare UNC13B variations and risk of schizophrenia: Whole-exome sequencing in a multiplex family and follow-up resequencing and a case-control study
Ethanol treatment of lymphoblastoid cell lines from alcoholics and non-alcoholics causes many subtle changes in gene expression
The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists
GABA/Glutamate synaptic pathways targeted by integrative genomic and electrophysiological explorations distinguish autism from intellectual disability
Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders
Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin
Gestational and early postnatal hypothyroidism alters VGluT1 and VGAT bouton distribution in the neocortex and hippocampus, and behavior in rats
An evo-devo approach to thyroid hormones in cerebral and cerebellar cortical development: etiological implications for autism
Integrating multiple genomic data to predict disease-causing nonsynonymous single nucleotide variants in exome sequencing studies
The effect of paternal age on offspring intelligence and personality when controlling for paternal trait level
Human variants in the neuronal basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function
Integrated model of de novo and inherited genetic variants yields greater power to identify risk genes
Network topologies and convergent aetiologies arising from deletions and duplications observed in individuals with autism
Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with autism spectrum disorder
A simple method for analyzing exome sequencing data shows distinct levels of nonsynonymous variation for human immune and nervous system genes
Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel
Identification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large ASD population
Environmental and state-level regulatory factors affect the incidence of autism and intellectual disability
Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments
Misregulation of an Activity-Dependent Splicing Network as a Common Mechanism Underlying Autism Spectrum Disorders
Vitamin D-related genes are subjected to significant de novo mutation burdens in autism spectrum disorder
Identification of novel mutations in the HbF repressor gene BCL11A in patients with autism and intelligence disabilities
L1 coupling to ankyrin and the spectrin-actin cytoskeleton modulates ethanol inhibition of L1 adhesion and ethanol teratogenesis
Advances in Genetic Discovery and Implications for Counseling of Patients and Families with Autism Spectrum Disorders
Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk
An Ankyrin-G N-terminal Gate and Protein Kinase CK2 Dually Regulate Binding of Voltage-gated Sodium and KCNQ2/3 Potassium Channels
Changes in the Fluorescence Tracking of NaV1.6 Protein Expression in a BTBR T+Itpr3tf/J Autistic Mouse Model
Disruption of the psychiatric risk gene Ankyrin 3 enhances microtubule dynamics through GSK3/CRMP2 signaling
Overrepresentation of genetic variation in the AnkyrinG interactome is related to a range of neurodevelopmental disorders.
DNA methylation signatures of adolescent victimization: analysis of a longitudinal monozygotic twin sample
Autism: Treatment Targets
The absence of effective treatments for autism are due to the high clinical and genetic heterogeneity between affected individuals, restricted knowledge of the underlying pathophysiological mechanisms, and the lack of reliable diagnostic biomarkers. Identification of more homogenous biological subgroups is therefore essential for the development of novel treatments based on the molecular mechanisms underpinning autism and autism spectrum disorders. Find the latest research on autism treatment targets here.
Central Nervous System Vasculitis
Central nervous system vasculitis is a newly recognized inflammatory brain disease, which may develop as a primary condition, or secondary to an underlying systemic disease. Here is the latest research.
Bipolar disorder is characterized by manic and/or depressive episodes and associated with uncommon shifts in mood, activity levels, and energy. Discover the latest research this illness here.
Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research.