---
_id: '10281'
abstract:
- lang: eng
  text: Mutations affecting mTOR or RAS signaling underlie defined syndromes (the
    so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder
    (ASD). These syndromes show a broad variety of somatic phenotypes including cancers,
    skin abnormalities, heart disease and facial dysmorphisms. Less well studied are
    the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these
    signalopathies in ASD reviewing genetic, human cell model, rodent studies and
    clinical trials. We conclude that signalopathies have an increased liability for
    ASD and that, in particular, ASD individuals with dysmorphic features and intellectual
    disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related
    genes. Studies on rodent and human cell models confirm aberrant neuronal development
    as the underlying pathology. Human studies further suggest that multiple hits
    are necessary to induce the respective phenotypes. Recent clinical trials do only
    report improvements for comorbid conditions such as epilepsy or cancer but not
    for behavioral aspects. Animal models show that treatment during early development
    can rescue behavioral phenotypes. Taken together, we suggest investigating the
    differential roles of mTOR and RAS signaling in both human and rodent models,
    and to test drug treatment both during and after neuronal development in the available
    model systems
acknowledgement: 'This review was funded by the IMI2 Initiative under the grant AIMS-2-TRIALS
  No 777394, by the Hessian Ministry for Science and Arts; State of Hesse Ministry
  for Science and Arts: LOEWE-Grant to the CePTER-Consortium (www.uni-frankfurt.de/67689811);
  Research (BMBF) under the grant RAISE-genic No 779282 all to AGC. This work was
  also supported by the European Union’s Horizon 2020 research and innovation program
  (ERC) grant 715508 (REVERSEAUTISM) and by the Austrian Science Fund (FWF) (DK W1232-B24)
  both to G.N. and both BMBF GeNeRARe 01GM1519A and CRC 1080, project B10, of the
  German Research Foundation (DFG) to M.J.S, respectively. We want to thank R. Waltes
  for her support in preparing this manuscript.'
alternative_title:
- Special Issue "From Genes to Therapy in Autism Spectrum Disorder"
article_number: '1746'
article_processing_charge: No
article_type: original
author:
- first_name: Verica
  full_name: Vasic, Verica
  last_name: Vasic
- first_name: Mattson S.O.
  full_name: Jones, Mattson S.O.
  last_name: Jones
- first_name: Denise
  full_name: Haslinger, Denise
  id: 76922BDA-3D3B-11EA-90BD-A44F3DDC885E
  last_name: Haslinger
- first_name: Lisa
  full_name: Knaus, Lisa
  id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
  last_name: Knaus
- first_name: Michael J.
  full_name: Schmeisser, Michael J.
  last_name: Schmeisser
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Andreas G.
  full_name: Chiocchetti, Andreas G.
  last_name: Chiocchetti
citation:
  ama: 'Vasic V, Jones MSO, Haslinger D, et al. Translating the role of mtor-and ras-associated
    signalopathies in autism spectrum disorder: Models, mechanisms and treatment.
    <i>Genes</i>. 2021;12(11). doi:<a href="https://doi.org/10.3390/genes12111746">10.3390/genes12111746</a>'
  apa: 'Vasic, V., Jones, M. S. O., Haslinger, D., Knaus, L., Schmeisser, M. J., Novarino,
    G., &#38; Chiocchetti, A. G. (2021). Translating the role of mtor-and ras-associated
    signalopathies in autism spectrum disorder: Models, mechanisms and treatment.
    <i>Genes</i>. MDPI. <a href="https://doi.org/10.3390/genes12111746">https://doi.org/10.3390/genes12111746</a>'
  chicago: 'Vasic, Verica, Mattson S.O. Jones, Denise Haslinger, Lisa Knaus, Michael
    J. Schmeisser, Gaia Novarino, and Andreas G. Chiocchetti. “Translating the Role
    of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models,
    Mechanisms and Treatment.” <i>Genes</i>. MDPI, 2021. <a href="https://doi.org/10.3390/genes12111746">https://doi.org/10.3390/genes12111746</a>.'
  ieee: 'V. Vasic <i>et al.</i>, “Translating the role of mtor-and ras-associated
    signalopathies in autism spectrum disorder: Models, mechanisms and treatment,”
    <i>Genes</i>, vol. 12, no. 11. MDPI, 2021.'
  ista: 'Vasic V, Jones MSO, Haslinger D, Knaus L, Schmeisser MJ, Novarino G, Chiocchetti
    AG. 2021. Translating the role of mtor-and ras-associated signalopathies in autism
    spectrum disorder: Models, mechanisms and treatment. Genes. 12(11), 1746.'
  mla: 'Vasic, Verica, et al. “Translating the Role of Mtor-and Ras-Associated Signalopathies
    in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” <i>Genes</i>,
    vol. 12, no. 11, 1746, MDPI, 2021, doi:<a href="https://doi.org/10.3390/genes12111746">10.3390/genes12111746</a>.'
  short: V. Vasic, M.S.O. Jones, D. Haslinger, L. Knaus, M.J. Schmeisser, G. Novarino,
    A.G. Chiocchetti, Genes 12 (2021).
date_created: 2021-11-14T23:01:24Z
date_published: 2021-10-30T00:00:00Z
date_updated: 2023-08-14T11:46:12Z
day: '30'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3390/genes12111746
ec_funded: 1
external_id:
  isi:
  - '000834044200002'
file:
- access_level: open_access
  checksum: 256cb832a9c3051c7dc741f6423b8cbd
  content_type: application/pdf
  creator: dernst
  date_created: 2022-05-16T07:02:27Z
  date_updated: 2022-05-16T07:02:27Z
  file_id: '11380'
  file_name: 2021_Genes_Vasic.pdf
  file_size: 1335308
  relation: main_file
  success: 1
file_date_updated: 2022-05-16T07:02:27Z
has_accepted_license: '1'
intvolume: '        12'
isi: 1
issue: '11'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '10'
oa: 1
oa_version: Published Version
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
publication: Genes
publication_identifier:
  eissn:
  - 2073-4425
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Translating the role of mtor-and ras-associated signalopathies in autism spectrum
  disorder: Models, mechanisms and treatment'
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...