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Article
Open AccessTracing the invisible mutant ADNP protein in Helsmoortel-Van der Aa syndrome patients
Heterozygous de novo mutations in the Activity-Dependent Neuroprotective Homeobox (ADNP) gene underlie Helsmoortel-Van der Aa syndrome (HVDAS). Most of these mutations are situated in the last exon and we previou...
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Article
Prevalence of comorbidities in individuals with neurodevelopmental disorders from the aggregated phenomics data of 51,227 pediatric individuals
The prevalence of comorbidities in individuals with neurodevelopmental disorders (NDDs) is not well understood, yet these are important for accurate diagnosis and prognosis in routine care and for characterizi...
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Article
Open AccessADNP dysregulates methylation and mitochondrial gene expression in the cerebellum of a Helsmoortel–Van der Aa syndrome autopsy case
Helsmoortel–Van der Aa syndrome is a neurodevelopmental disorder in which patients present with autism, intellectual disability, and frequent extra-neurological features such as feeding and gastrointestinal pr...
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Article
PhenoScore quantifies phenotypic variation for rare genetic diseases by combining facial analysis with other clinical features using a machine-learning framework
Several molecular and phenotypic algorithms exist that establish genotype–phenotype correlations, including facial recognition tools. However, no unified framework that investigates both facial data and other ...
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Article
Open AccessChromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism
Individuals affected with autism often suffer additional co-morbidities such as intellectual disability. The genes contributing to autism cluster on a relatively limited number of cellular pathways, including ...
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Article
Vineland Adaptive Behavior Scale in a Cohort of Four ADNP Syndrome Patients Implicates Age-Dependent Developmental Delays with Increased Impact of Activities of Daily Living
Activity-dependent neuroprotective protein (ADNP) is one of the lead genes in autism spectrum disorder/intellectual disability. Heterozygous, de novo ADNP mutations cause the ADNP syndrome. Here, to evaluate n...
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Article
Open AccessDiscovery of autism/intellectual disability somatic mutations in Alzheimer's brains: mutated ADNP cytoskeletal impairments and repair as a case study
With Alzheimer’s disease (AD) exhibiting reduced ability of neural stem cell renewal, we hypothesized that de novo mutations controlling embryonic development, in the form of brain somatic mutations instigate ...
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Article
Open AccessAbundancy of polymorphic CGG repeats in the human genome suggest a broad involvement in neurological disease
Expanded CGG-repeats have been linked to neurodevelopmental and neurodegenerative disorders, including the fragile X syndrome and fragile X-associated tremor/ataxia syndrome (FXTAS). We hypothesized that as of...
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Open AccessAuthor Correction: Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
Open AccessLarge-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case–control mutation burden analysis is unestablished. Here, w...
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Article
Open AccessTauopathy in the young autistic brain: novel biomarker and therapeutic target
Given our recent discovery of somatic mutations in autism spectrum disorder (ASD)/intellectual disability (ID) genes in postmortem aged Alzheimer’s disease brains correlating with increasing tauopathy, it is i...
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Article
Open AccessReduced serum levels of pro-inflammatory chemokines in fragile X syndrome
Fragile X syndrome (FXS) is the most frequent cause of inherited intellectual disability and the most commonly identified monogenic cause of autism. Recent studies have shown that long-term pathological conseq...
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Article
Open AccessFrameshift mutations at the C-terminus of HIST1H1E result in a specific DNA hypomethylation signature
We previously associated HIST1H1E mutations causing Rahman syndrome with a specific genome-wide methylation pattern.
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Article
Fragile X syndrome
Fragile X syndrome (FXS) is the leading inherited form of intellectual disability and autism spectrum disorder, and patients can present with severe behavioural alterations, including hyperactivity, impulsivit...
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Article
Open AccessA randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome
Gamma-aminobutyric acid (GABA) system deficits are integral to the pathophysiologic development of fragile X syndrome (FXS). Ganaxolone, a GABAA receptor positive allosteric modulator, is hypothesized to improve ...
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Article
Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains
This study characterizes the properties of disease-causing mutations that produce sporadic amino acid replacements in proteins of people with autism and developmental delay. The mutations tend to cluster and r...
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Article
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases
Evan Eichler and colleagues use single-molecule molecular-inversion probes to sequence the coding and splicing regions of 208 candidate genes in more than 11,730 individuals with neurodevelopmental disorders. ...
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Article
Open AccessVariantDB: a flexible annotation and filtering portal for next generation sequencing data
Interpretation of the multitude of variants obtained from next generation sequencing (NGS) is labor intensive and complex. Web-based interfaces such as Galaxy streamline the generation of variant lists but lac...
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Article
A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP
Frank Kooy, Nathalie Van der Aa and colleagues report that de novo mutations in ADNP cause a syndrome characterized by autism, intellectual disability and facial dysmorphisms. ADNP encodes a transcription factor ...
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Article
Metabonomics adds a new dimension to fragile X syndrome
Fragile X syndrome is the most common cause of inherited intellectual disability, but the underlying pathophysiology is complex and effective treatments are lacking. In a recent study of fragile X mental retardat...
