---
OA_place: publisher
_id: '395'
abstract:
- lang: eng
text: 'Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping
with other neurological conditions. Despite the remarkable number of scientific
breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders
(e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great
challenge. Recent advancements in geno mics, like whole-exome or whole-genome
sequencing, have enabled scientists to identify numerous mutations underlying
neurodevelopmental disorders. Given the few hundred risk genes that were discovered,
the etiological variability and the heterogeneous phenotypic outcomes, the need
for genotype -along with phenotype- based diagnosis of individual patients becomes
a requisite. Driven by this rationale, in a previous study our group described
mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding
for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause
of ASD. Following up on the role of BCAAs, in the study described here we show
that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter
localized mainly at the blood brain barrier (BBB), has an essential role in maintaining
normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial
cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation
and severe neurolo gical abnormalities. Additionally, deletion of Slc7a5 from
the neural progenitor cell population leads to microcephaly. Interestingly, we
demonstrate that BCAA intracerebroventricular administration ameliorates abnormal
behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients
diagnosed with neurological dis o r ders helped us identify several patients with
autistic traits, microcephaly and motor delay carrying deleterious homozygous
mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological
syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA
s in human bra in function. Together with r ecent studies (described in chapter
two) that have successfully made the transition into clinical practice, our findings
on the role of B CAAs might have a crucial impact on the development of novel
individualized therapeutic strategies for ASD. '
acknowledged_ssus:
- _id: PreCl
- _id: EM-Fac
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Dora-Clara
full_name: Tarlungeanu, Dora-Clara
id: 2ABCE612-F248-11E8-B48F-1D18A9856A87
last_name: Tarlungeanu
citation:
ama: Tarlungeanu D-C. The branched chain amino acids in autism spectrum disorders
. 2018. doi:10.15479/AT:ISTA:th_992
apa: Tarlungeanu, D.-C. (2018). The branched chain amino acids in autism spectrum
disorders . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_992
chicago: Tarlungeanu, Dora-Clara. “The Branched Chain Amino Acids in Autism Spectrum
Disorders .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_992.
ieee: D.-C. Tarlungeanu, “The branched chain amino acids in autism spectrum disorders
,” Institute of Science and Technology Austria, 2018.
ista: Tarlungeanu D-C. 2018. The branched chain amino acids in autism spectrum disorders
. Institute of Science and Technology Austria.
mla: Tarlungeanu, Dora-Clara. The Branched Chain Amino Acids in Autism Spectrum
Disorders . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_992.
short: D.-C. Tarlungeanu, The Branched Chain Amino Acids in Autism Spectrum Disorders
, Institute of Science and Technology Austria, 2018.
corr_author: '1'
date_created: 2018-12-11T11:46:14Z
date_published: 2018-03-01T00:00:00Z
date_updated: 2026-04-08T14:15:20Z
day: '01'
ddc:
- '570'
- '616'
degree_awarded: PhD
department:
- _id: GaNo
doi: 10.15479/AT:ISTA:th_992
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creator: dernst
date_created: 2019-04-05T09:19:17Z
date_updated: 2021-02-11T23:30:15Z
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date_created: 2019-04-05T09:19:17Z
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has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: '88'
project:
- _id: 25473368-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: F03523
name: Transmembrane Transporters in Health and Disease
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '7434'
pubrep_id: '992'
related_material:
record:
- id: '1183'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
title: 'The branched chain amino acids in autism spectrum disorders '
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2018'
...