Publications by authors named "Maria Chahrour"

Perturb-seq is a powerful approach to systematically assess how genes and enhancers impact the molecular and cellular pathways of development and disease. However, technical challenges have limited its application in stem cell-based systems. Here, we benchmarked Perturb-seq across multiple CRISPRi modalities, on diverse genomic targets, in multiple human pluripotent stem cells, during directed differentiation to multiple lineages, and across multiple sgRNA delivery systems.

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Article Synopsis
  • - The study focused on understanding the genetic causes of autism spectrum disorder (ASD) by sequencing the DNA of 754 individuals from 195 families, identifying a total of 38,834 new genetic variants.
  • - Researchers discovered 92 potentially harmful genetic variations in 73 known genes among 68 individuals with ASD, along with 158 likely damaging variants in 120 other candidate genes.
  • - The findings enhance our knowledge of ASD genetics, revealing patterns linked to brain development and cellular signaling, which could aid in diagnosing and developing treatments for the disorder.
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The landscape of autism spectrum disorder (ASD) in Lebanon is unique because of high rates of consanguinity, shared ancestry, and increased remote consanguinity. ASD prevalence in Lebanon is 1 in 68 with a male-to-female ratio of 2:1. This study aims to investigate the impact of an inherited deletion in UBLCP1 (Ubiquitin-Like Domain-Containing CTD Phosphatase 1) on the ubiquitin-proteasome system (UPS) and proteolysis.

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Chromatin regulation plays a pivotal role in establishing and maintaining cellular identity and is one of the top pathways disrupted in autism spectrum disorder (ASD). The hippocampus, composed of distinct cell types, is often affected in patients with ASD. However, the specific hippocampal cell types and their transcriptional programs that are dysregulated in ASD are unknown.

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Hereditary spastic parapareses (HSPs) are clinically heterogeneous motor neuron diseases with variable age of onset and severity. Although variants in dozens of genes are implicated in HSPs, much of the genetic basis for pediatric-onset HSP remains unexplained. Here, we re-analyzed clinical exome-sequencing data from siblings with HSP of unknown genetic etiology and identified an inherited nonsense mutation (c.

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Autism spectrum disorder (ASD) is a group of complex neurodevelopmental conditions affecting communication and social interaction in 2.3% of children. Studies that demonstrated its complex genetic architecture have been mainly performed in populations of European ancestry.

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in communication, diminished social skills, and restrictive and repetitive behaviors and interests. ASD affects approximately 2.3% of the population and is highly heterogeneous, both phenotypically and genetically.

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Autism spectrum disorder (ASD) is a collection of neurodevelopmental disorders characterized by deficits in social communication and restricted, repetitive patterns of behavior or interests. ASD is highly heritable, but genetically and phenotypically heterogeneous, reducing the power to identify causative genes. We performed whole genome sequencing (WGS) in an ASD cohort of 68 individuals from 22 families enriched for recent shared ancestry.

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Background: Autism spectrum disorder (ASD) continues to climb in prevalence worldwide. Developed nations have focused on aligning their medical and research communities in order to investigate the mechanisms of pathogenesis, diagnosis, and societal impact of this disorder. A simultaneous rise of ASD has impacted developing nations, such as Ethiopia, without a commensurate ability to research the knowledge, beliefs, resources, and training regarding this condition in the country.

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Article Synopsis
  • * Researchers found a gene called KDM5A by studying mice that had trouble making sounds, and when they turned off this gene in mice, the mice stopped vocalizing and showed other problems like being less social and having trouble thinking.
  • * They also looked at the genes of humans with ASD who can't speak and found some changes in the KDM5A gene, which shows how important this gene is for how the brain develops and works.
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More than 98% of the human genome is made up of non-coding DNA, but techniques to ascertain its contribution to human disease have lagged far behind our understanding of protein coding variations. Autism spectrum disorder (ASD) has been mostly associated with coding variations via de novo single nucleotide variants (SNVs), recessive/homozygous SNVs, or de novo copy number variants (CNVs); however, most ASD cases continue to lack a genetic diagnosis. We analyzed 187 consanguineous ASD families for biallelic CNVs.

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Kaufman oculocerebrofacial syndrome (KOS) is a recessive neurodevelopmental disorder characterized by intellectual disability and lack of speech. KOS is caused by inactivating mutations in , but the underlying biological mechanisms are completely unknown. We found that loss of in mice resulted in growth retardation, decreased grip strength, and loss of vocalization.

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Protein homeostasis is tightly regulated by the ubiquitin proteasome pathway. Disruption of this pathway gives rise to a host of neurological disorders. Through whole exome sequencing (WES) in families with neurodevelopmental disorders, we identified mutations in PSMD12, a core component of the proteasome, underlying a neurodevelopmental disorder with intellectual disability (ID) and features of autism spectrum disorder (ASD).

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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with multiple comorbidities, including intellectual disability, anxiety, and epilepsy. Evidence that ASD is highly heritable has spurred major efforts to unravel its genetics, revealing possible contributions from hundreds of genes through rare and common variation and through copy-number changes.

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The ubiquitin proteasome system (UPS) is a highly conserved pathway that tightly regulates protein turnover in cells. This process is integral to neuronal development, differentiation, and function. Several members of the UPS are disrupted in neuropsychiatric disorders, highlighting the importance of this pathway in brain development and function.

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Sequencing studies have implicated haploinsufficiency of , a SWI/SNF chromatin-remodeling subunit, in short stature (Yu et al., 2015), autism spectrum disorder (O'Roak et al., 2012), intellectual disability (Deciphering Developmental Disorders Study, 2015), and corpus callosum agenesis (Halgren et al.

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Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages.

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Article Synopsis
  • Gain-of-function mutations in certain genes can lead to neurodegenerative diseases, while loss-of-function mutations in the same genes create different effects; ATXN1 protein involvement is a key example.
  • The study reveals that the ATXN1-CIC complex is crucial for survival and brain development, as its absence can lead to hyperactivity, learning difficulties, and abnormal neuron development.
  • Researchers identified individuals with specific mutations in CIC showing patterns of intellectual disability, ADHD, and autism, indicating that the loss of ATXN1-CIC complexes results in a range of neurobehavioral issues.
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To describe pontine axonal anomalies across diverse brain malformations. Institutional review board-approved review of magnetic resonance imaging (MRI) and genetic testing of 31 children with brain malformations and abnormal pons by diffusion tensor imaging. Anomalous dorsal pontocerebellar tracts were seen in mid-hindbrain anomalies and in diffuse malformations of cortical development including lissencephaly, gyral disorganization with dysplastic basal ganglia, presumed congenital fibrosis of extraocular muscles type 3, and in callosal agenesis without malformations of cortical development.

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Autism spectrum disorder (ASD) is a constellation of neurodevelopmental presentations with high heritability and both phenotypic and genetic heterogeneity. To date, mutations in hundreds of genes have been associated to varying degrees with increased ASD risk. A better understanding of the functions of these genes and whether they fit together in functional groups or impact similar neuronal circuits is needed to develop rational treatment strategies.

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Sensory stimuli drive the maturation and function of the mammalian nervous system in part through the activation of gene expression networks that regulate synapse development and plasticity. These networks have primarily been studied in mice, and it is not known whether there are species- or clade-specific activity-regulated genes that control features of brain development and function. Here we use transcriptional profiling of human fetal brain cultures to identify an activity-dependent secreted factor, Osteocrin (OSTN), that is induced by membrane depolarization of human but not mouse neurons.

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Class I histone deacetylases (HDACs) Hdac1 and Hdac2 can associate together in protein complexes with transcriptional factors such as methyl-CpG-binding protein 2 (MeCP2). Given their high degree of sequence identity, we examined whether Hdac1 and Hdac2 were functionally redundant in mature mouse brain. We demonstrate that postnatal forebrain-specific deletion of both Hdac1 and Hdac2 in mice impacts neuronal survival and results in an excessive grooming phenotype caused by dysregulation of Sap90/Psd95-associated protein 3 (Sapap3; also known as Dlgap3) in striatum.

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