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Article
Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy
We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants...
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Article
Open AccessSCIP: software for efficient clinical interpretation of copy number variants detected by whole-genome sequencing
Copy number variants (CNVs) represent major etiologic factors in rare genetic diseases. Current clinical CNV interpretation workflows require extensive back-and-forth with multiple tools and databases. This in...
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Article
Open AccessDisruption of DDX53 coding sequence has limited impact on iPSC-derived human NGN2 neurons
The X-linked PTCHD1 locus is strongly associated with autism spectrum disorder (ASD). Males who carry chromosome microdeletions of PTCHD1 antisense long non-coding RNA (PTCHD1-AS)/DEAD-box helicase 53 (DDX53) hav...
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Article
Open AccessGenome-wide rare variant score associates with morphological subtypes of autism spectrum disorder
Defining different genetic subtypes of autism spectrum disorder (ASD) can enable the prediction of developmental outcomes. Based on minor physical and major congenital anomalies, we categorize 325 Canadian chi...
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Article
Open AccessMutations in trpγ, the homologue of TRPC6 autism candidate gene, causes autism-like behavioral deficits in Drosophila
Autism Spectrum Disorder (ASD) is characterized by impaired social communication, restricted interests, and repetitive and stereotyped behaviors. The TRPC6 (transient receptor potential channel 6) represents an A...
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Article
Open AccessRare CACNA1H and RELN variants interact through mTORC1 pathway in oligogenic autism spectrum disorder
Oligogenic inheritance of autism spectrum disorder (ASD) has been supported by several studies. However, little is known about how the risk variants interact and converge on causative neurobiological pathways....
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Article
Open AccessChromosomal microarray analysis of 410 Han Chinese patients with autism spectrum disorder or unexplained intellectual disability and developmental delay
Copy number variants (CNVs) are recognized as a crucial genetic cause of neurodevelopmental disorders (NDDs). Chromosomal microarray analysis (CMA), the first-tier diagnostic test for individuals with NDDs, ha...
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Article
Open AccessSingle-cell transcriptome identifies molecular subtype of autism spectrum disorder impacted by de novo loss-of-function variants regulating glial cells
In recent years, several hundred autism spectrum disorder (ASD) implicated genes have been discovered impacting a wide range of molecular pathways. However, the molecular underpinning of ASD, particularly from...
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Article
Open AccessHomozygous duplication identified by whole genome sequencing causes LRBA deficiency
In more than one-third of primary immunodeficiency (PID) patients, extensive genetic analysis including whole-exome sequencing (WES) fails to identify the genetic defect. Whole-genome sequencing (WGS) is able ...
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Article
Open AccessA recurrent SHANK3 frameshift variant in Autism Spectrum Disorder
Autism Spectrum Disorder (ASD) is genetically complex with ~100 copy number variants and genes involved. To try to establish more definitive genotype and phenotype correlations in ASD, we searched genome seque...
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Article
Open AccessRCL1 copy number variants are associated with a range of neuropsychiatric phenotypes
Mendelian and early-onset severe psychiatric phenotypes often involve genetic variants having a large effect, offering opportunities for genetic discoveries and early therapeutic interventions. Here, the index...
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Article
Open AccessAncestry and frequency of genetic variants in the general population are confounders in the characterization of germline variants linked to cancer
Pediatric high-grade gliomas (pHGGs) are incurable malignant brain cancers. Clear somatic genetic drivers are difficult to identify in the majority of cases. We hypothesized that this may be due to the existen...
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Article
Open AccessA large data resource of genomic copy number variation across neurodevelopmental disorders
Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among N...
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Article
Open AccessExpanding the neurodevelopmental phenotypes of individuals with de novo KMT2A variants
De novo loss-of-function (LoF) variants in the KMT2A gene are associated with Wiedemann−Steiner Syndrome (WSS). Recently, de novo KMT2A variants have been identified in sequencing studies of cohorts of individual...
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Article
Open AccessA genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees
Although several genetic variants for autism spectrum disorder (ASD) have now been identified, these largely occur sporadically or are de novo. Much less progress has been made in identifying inherited variant...
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Article
Open AccessMutations in RAB39B in individuals with intellectual disability, autism spectrum disorder, and macrocephaly
Autism spectrum disorder (ASD), a developmental disorder of early childhood onset, affects males four times more frequently than females, suggesting a role for the sex chromosomes. In this study, we describe a...
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Article
Open AccessVariable phenotype expression in a family segregating microdeletions of the NRXN1 and MBD5 autism spectrum disorder susceptibility genes
Autism spectrum disorder is a developmental condition of early childhood onset, which impacts socio-communicative functioning and is principally genetic in etiology. Currently, more than 50 genomic loci are de...
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Article
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
Yuen et al. developed a cloud-based database with 5,205 whole genomes from families with autism spectrum disorder (ASD). They identified 18 new candidate ASD-risk genes and approximately 100 risk genes and copy-n...
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Article
Open AccessUncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation
Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit differ...
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Article
Open AccessGenome-wide characteristics of de novo mutations in autism
De novo mutations (DNMs) are important in autism spectrum disorder (ASD), but so far analyses have mainly been on the ~1.5% of the genome encoding genes. Here, we performed whole-genome sequencing (WGS) of 200 AS...
