Publications by authors named "Claire Leblond"
Autism represents a large spectrum of diverse individuals with varying underlying genetic architectures and needs. For some individuals, a single de novo or ultrarare genetic variant has a large effect on the intensity of specific dimensions of the phenotype, while, for others, a combination of thousands of variants commonly found in the general population are involved. The variants with large impact are found in up to 30% of autistic individuals presenting with intellectual disability, significant speech delay, motor delay, and/or seizures.
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- Autism is a common condition influenced by both single gene issues and multiple genes, and many autistic people need better healthcare that genomics can help provide.
- The European Autism GEnomics Registry (EAGER) aims to collect info about autistic people who have had their entire DNA sequenced to help with future research and trials.
- EAGER will involve 1,500 participants from 13 places in 8 countries who will share genetic samples and fill out surveys to help researchers understand the link between genetics and health.
Article Synopsis
- Over 100 genes are linked to autism, but the prevalence of rare genetic variants in people without an autism diagnosis is not well understood.
- This study analyzed data from over 13,000 individuals with autism and 210,000 without, finding that rare loss-of-function variants in autism-associated genes negatively impact intelligence, education, and income.
- Brain imaging data showed no significant anatomical differences related to these variants, suggesting a need for more research on how genetic factors influence individual experiences beyond autism diagnosis.
Article Synopsis
- * A study followed 333 individuals (161 autistic and 172 neurotypical) over 12-24 months, assessing their behavior and brain structure to understand variations in adaptive behavior within autism.
- * Results revealed distinct brain structure profiles associated with different adaptive behavior outcomes in autistic participants, potentially linked to autism-related genes, which could inform targeted interventions for individuals with poorer outcomes.
Article Synopsis
- SHANK3-related Phelan-McDermid syndrome (PMS) arises from the loss of part of chromosome 22, impacting the SHANK3 gene, leading to a range of symptoms like developmental delay, language issues, autism, and epilepsy.
- Genetic variations, including different sizes of deletions, can affect how severely these symptoms manifest in patients, indicating that not all cases of PMS involve SHANK3 directly.
- The review highlights 110 genes in the 22q13 region that may play a role in neurodevelopmental disorders, suggesting the need for future studies to better understand these connections and improve care for PMS patients.
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- The study investigates sensory processing issues in autistic individuals, focusing on hypo and hyper-sensory sensitivities potentially linked to genetic factors affecting GABA-ergic and glutamatergic pathways.
- Researchers analyzed the sensory profiles of 1136 participants (including autistic individuals, relatives, and controls) and found significant differences in sensory processing between these groups, with variability being a key factor.
- While the new differential Short Sensory Profile (dSSP) provided useful insights, it struggled to distinguish between individuals with similar sensory symptom levels, suggesting a need for combining this score with genetic and other sensory assessments for better understanding of sensory processing in autism.
Article Synopsis
- - Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition marked by challenges in social communication and varying individual characteristics, making targeted treatments essential.
- - A study involving 436 individuals analyzed neural responses to faces and found that children and adults with ASD had slower early brain activity (N170 latency) compared to those without ASD, which correlated with social functioning and prognosis.
- - Findings suggest that measuring N170 latency can effectively stratify different subgroups within ASD, offering potential for improved personalized treatment approaches based on biological and social outcome predictions.
Article Synopsis
- The study explored genetic variations among 12,893 autistic individuals to better understand the link between genetics and the diverse features of autism.
- Researchers identified six key factors related to core autism traits, finding that while common genetic variants were linked to these traits, de novo variants were not.
- The analysis revealed that higher autism polygenic scores (PGS) correlate with a lower chance of co-occurring developmental disabilities, particularly showing that autistic females without intellectual disability inherit more genetic traits than males.
Article Synopsis
- Autism Spectrum Disorder (ASD) shows a range of outcomes, with some individuals improving and others not, emphasizing the need for personalized medicine approaches based on biological processes.
- A longitudinal study involving 483 individuals assessed behavioral, neuroanatomical, and genetic data to categorize those with ASD into outcome groups: "increasers," "no-changers," and "decreasers."
- Results revealed distinct neuroanatomical features in these groups, indicating that deviations from a typical neuroanatomical profile can predict individual outcomes, linked to genetic factors related to brain development.
Article Synopsis
- - The study investigates the link between brain anatomy and genetics in individuals with autism spectrum disorder (ASD), focusing on differences in cortical thickness across a diverse group of participants.
- - Results show significant differences in key brain regions between those with ASD and typically developing individuals, revealing neuroanatomical deviations that correlate with genetic predisposition and symptom severity.
- - Findings support the connection between brain structure and the molecular mechanisms involved in ASD, suggesting pathways for tailored therapeutic interventions and better understanding of the disorder's complexity.
Article Synopsis
- The study of neurodevelopmental disorders (NDD) has advanced significantly, identifying over 1,500 genes linked to conditions like autism and intellectual disability.
- Researchers are investigating these genes to understand how mutations affect individuals and to compile databases that facilitate this research.
- A list of high confidence NDD genes (N=1,586) has been created, which is important for analyzing large datasets and diagnostics, but there's a need for better data on mutation carriers to enhance understanding of these disorders.
Article Synopsis
- Hyperserotonemia, a common biochemical anomaly in autism spectrum disorders (ASD), has not been fully understood, prompting this study to explore serotonin sulfation by phenol sulfotransferases (PST) in blood samples from individuals with ASD and their families compared to controls.
- The study found significantly reduced activity of two PST isoforms in platelets of ASD individuals, linking deficiencies in PST-M to higher serotonin levels and confirming similar deficits in pineal gland tissues, a key source of serotonin.
- Although genetic analyses of SULT1A genes did not connect variations to PST activity or ASD risk, broader investigations revealed impairments in other sulfation markers, suggesting a generalized issue in sulfation metabolism that may explain hyperser
"Oligogenic inheritance" is used to describe cases where more than one rare pathogenic variant is observed in the same individual. While multiple variants can alter disease presentation, the necessity of multiple variants to instigate pathogenesis has not been addressed in amyotrophic lateral sclerosis (ALS). We sequenced ALS-associated genes in C9orf72-expansion-positive and negative ALS patients, alongside unaffected controls, to test the importance of oligogenicity and variant deleteriousness in ALS.
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- The core diagnostic criteria for autism involve difficulties in social communication and the presence of repetitive behaviors, with evidence suggesting these aspects may be genetically distinct.
- A study involving over 51,000 participants found that systemising—a non-social trait related to autism—is heritable and has a genetic connection to autism, particularly with restricted behaviors.
- The research indicates that while systemising is linked to repetitive behaviors in autism, it shows no significant connection to social difficulties, supporting the idea that the two core domains of autism are genetically separate.
Article Synopsis
- The text refers to a correction made to a previously published article with the DOI 10.1038/s41525-017-0035-2.
- The correction likely addresses errors or omissions in the original publication.
- This ensures that readers have access to accurate and updated information related to the research discussed in the article.
Objective: To test for somatic hexanucleotide repeat expansion (HRE) and hexanucleotide repeat length instability in the spinal cord of amyotrophic lateral sclerosis (ALS) cases.
Methods: Whole and partial spinal cords of 19 ALS cases were dissected into transversal sections (5 mm thick). The presence of HRE was tested in each independent section using RepeatPrimed PCR and amplicon-size genotyping.
Article Synopsis
- SMPD1 gene variants, particularly p.L302P and p.fsP330, are associated with an increased risk of developing Parkinson's disease (PD) in certain populations, specifically the Ashkenazi Jewish cohort.
- Analysis revealed that lower acid-sphingomyelinase activity in PD patients is linked to an earlier onset of the disease, indicating its potential role as a biomarker.
- Experimental findings showed that SMPD1 mutations disrupt the normal function of acid-sphingomyelinase, leading to higher levels of α-synuclein in dopaminergic cells, which may contribute to the pathogenesis of PD.
Article Synopsis
- A study examined 357 individuals from the Faroe Islands, including 36 with autism, to explore genetic associations with the condition.
- Findings showed that individuals with autism had a higher burden of rare genetic variants, inbreeding status, and more deleterious homozygous variants compared to non-autistic controls.
- The research identified new potentially harmful gene variants related to autism and emphasized the need for further understanding of how these genetic factors influence neuronal function.
Article Synopsis
- The SHANK3 protein plays a key role in the structure and function of excitatory synapses in the brain, and mutations in this gene have been linked to autism spectrum disorders (ASD).
- Researchers studied pyramidal neurons derived from patients with specific SHANK3 mutations and found that these neurons showed abnormal dendritic spine shapes and reduced density compared to healthy controls.
- The findings suggest that SHANK3 mutations contribute to synaptic abnormalities observed in some individuals with ASD, highlighting the importance of this gene in understanding the disorder.
Essential Tremor is a prevalent neurological disorder of unknown etiology. Studies suggest that genetic factors contribute to this pathology. To date, no causative mutations in a gene have been reproducibly reported.
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- * A study identified a rare homozygous deletion affecting specific genes (ELMOD3, CAPG, and SH2D6) in a boy with ASD, intellectual disability, and hearing impairment.
- * The findings suggest that the deletion may cause a new syndrome relating to hearing loss and autism/intellectual disability, emphasizing the role of ELMOD3 in hearing impairment and the potential effects of the deletions on brain development.
Background: MAPT haplotypes are associated with PD, but their association with rapid eye movement sleep behavior disorder is unclear.
Objective: To study the role of MAPT variants in rapid eye movement sleep behavior disorder.
Methods: Two cohorts were included: (A) PD (n = 600), rapid eye movement sleep behavior disorder (n = 613) patients, and controls (n = 981); (B) dementia with Lewy bodies patients with rapid eye movement sleep behavior disorder (n = 271) and controls (n = 950).
Article Synopsis
- Phelan-McDermid syndrome (PMS) is a genetic condition linked to deletions on chromosome 22q13, leading to symptoms like intellectual disability, speech delays, and autism spectrum disorders, with severity varying across individuals.
- The study involved analyzing 85 patients and found that 28% had abnormalities in the corpus callosum, a brain structure important for communication between hemispheres, and identified genomic regions that may contribute to specific symptoms like lack of speech.
- Additionally, researchers found significant genetic variations that might influence the severity of PMS and noted that some family members with the deletion could remain unaffected, indicating potential compensatory mechanisms for managing the disorder.
Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with a complex genetic architecture. They are characterized by impaired social communication, stereotyped behaviors and restricted interests and are frequently associated with comorbidities such as intellectual disability, epilepsy and severe sleep disorders. Hyperserotonemia and low melatonin levels are among the most replicated endophenotypes reported in ASD, but their genetic causes remain largely unknown.
View Article and Find Full Text PDFObjective: To assess the contribution of variants in , , and as essential tremor (ET) predisposing factors following their association in a 2-stage genome-wide association study (GWAS).
Methods: The coding regions of these genes was examined for the presence of rare variants using two approaches: (1) Looking at whole-exome and whole-genome sequencing data of 14 autosomal dominant multiplex ET families. (2) Conducting a targeted massive parallel sequencing to examine the three genes in cohorts of 269 ET cases and 287 control individuals.