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We are analyzing https://www.nature.com/articles/s41467-017-00933-6.

Title:
Variation in a range of mTOR-related genes associates with intracranial volume and intellectual disability | Nature Communications
Description:
De novo mutations in specific mTOR pathway genes cause brain overgrowth in the context of intellectual disability (ID). By analyzing 101 mMTOR-related genes in a large ID patient cohort and two independent population cohorts, we show that these genes modulate brain growth in health and disease. We report the mTOR activator gene RHEB as an ID gene that is associated with megalencephaly when mutated. Functional testing of mutant RHEB in vertebrate animal models indicates pathway hyperactivation with a concomitant increase in cell and head size, aberrant neuronal migration, and induction of seizures, concordant with the human phenotype. This study reveals that tight control of brain volume is exerted through a large community of mTOR-related genes. Human brain volume can be altered, by either rare disruptive events causing hyperactivation of the pathway, or through the collective effects of common alleles. The mTOR pathway is a key regulator of normal brain development. Here, the authors identify de novo mutations in RHEB, an mTOR activator protein, in patients with intellectual disability associated with megalencephaly and find a role for RHEB in regulating neuronal soma size and migration in vitro and in vivo.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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Keywords {🔍}

pubmed, genes, mtor, article, rheb, google, scholar, mutations, cas, brain, data, size, neuronal, mtorrelated, pathway, novo, patients, central, analysis, gene, supplementary, rapamycin, mice, geneset, significant, cohort, fig, nature, human, rhebppl, cell, studies, soma, control, rhebpsp, rhebwt, migration, cells, epilepsy, vector, nat, association, vivo, table, test, macrocephaly, seizures, performed, mutant, cortical,

Topics {✒️}

nature portfolio scientific research privacy policy special dietary service donkey anti-guinea-pig-alexa647 donkey anti-rabbit-alexa488-conjugated advertising pre-warmed trypsin/edta solution social media polygenic nature supplementary movie 1 translational repressor 4e-bp2 fvb/nhsd wild-type mice reprints gene annotation file guinea-pig anti map2 treatment-resistant focal-onset seizures nl/software/magma/ref_data/g1000_ceu nature 520 nature 493 nature 485 nature 467 nature log-rank mantel–cox test calculate gene-based p-values genome-wide snp data g-box residues characteristic dutch national e-infrastructure mtor-related gene-set based tweezer-type electrodes connected aging research mid2-related neurodevelopmental disabilities amino-acid residues mutated coordinating erk/mapk signalling institutional review board human wild-type67 mrna gtpase-activating protein complex cell-autonomous migration delay org/gsea/msigdb/genesets torc1-dependent epilepsy caused rapamycin-sensitive olfactory micronodules genome-wide summary statistics gene-wide p-values genome-wide association analyses free-floating coronal sections pi3k/akt/mtor signaling /download-enigma-gwas-results/ gene-specific mutation rates mowiol-dabco mounting medium mtor-related mutation carriers

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Schema {🗺️}

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         headline:Variation in a range of mTOR-related genes associates with intracranial volume and intellectual disability
         description:De novo mutations in specific mTOR pathway genes cause brain overgrowth in the context of intellectual disability (ID). By analyzing 101 mMTOR-related genes in a large ID patient cohort and two independent population cohorts, we show that these genes modulate brain growth in health and disease. We report the mTOR activator gene RHEB as an ID gene that is associated with megalencephaly when mutated. Functional testing of mutant RHEB in vertebrate animal models indicates pathway hyperactivation with a concomitant increase in cell and head size, aberrant neuronal migration, and induction of seizures, concordant with the human phenotype. This study reveals that tight control of brain volume is exerted through a large community of mTOR-related genes. Human brain volume can be altered, by either rare disruptive events causing hyperactivation of the pathway, or through the collective effects of common alleles. The mTOR pathway is a key regulator of normal brain development. Here, the authors identify de novo mutations in RHEB, an mTOR activator protein, in patients with intellectual disability associated with megalencephaly and find a role for RHEB in regulating neuronal soma size and migration in vitro and in vivo.
         datePublished:2017-10-20T00:00:00Z
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      headline:Variation in a range of mTOR-related genes associates with intracranial volume and intellectual disability
      description:De novo mutations in specific mTOR pathway genes cause brain overgrowth in the context of intellectual disability (ID). By analyzing 101 mMTOR-related genes in a large ID patient cohort and two independent population cohorts, we show that these genes modulate brain growth in health and disease. We report the mTOR activator gene RHEB as an ID gene that is associated with megalencephaly when mutated. Functional testing of mutant RHEB in vertebrate animal models indicates pathway hyperactivation with a concomitant increase in cell and head size, aberrant neuronal migration, and induction of seizures, concordant with the human phenotype. This study reveals that tight control of brain volume is exerted through a large community of mTOR-related genes. Human brain volume can be altered, by either rare disruptive events causing hyperactivation of the pathway, or through the collective effects of common alleles. The mTOR pathway is a key regulator of normal brain development. Here, the authors identify de novo mutations in RHEB, an mTOR activator protein, in patients with intellectual disability associated with megalencephaly and find a role for RHEB in regulating neuronal soma size and migration in vitro and in vivo.
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      dateModified:2017-10-20T00:00:00Z
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      sameAs:https://doi.org/10.1038/s41467-017-00933-6
      keywords:
         Development
         Genetics of the nervous system
         Genetics research
         Neurodevelopmental disorders
         Science
         Humanities and Social Sciences
         multidisciplinary
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