Brain Research Bulletin,
Год журнала:
2025,
Номер
227, С. 111411 - 111411
Опубликована: Май 29, 2025
Autism
Spectrum
Disorder
(ASD)
is
a
neurodevelopmental
condition
marked
by
difficulties
in
social
communication,
languages,
and
repetitive
behaviors.
Its
rising
prevalence
has
made
it
critical
global
public
health
issue.
ASD
believed
to
arise
from
combination
of
genetic
environmental
influences.
While
some
gene
mutations
associated
with
have
been
identified,
most
cases
lack
clear
explanations.
Evidence
increasingly
points
early-life
factors
as
key
contributors
ASD,
including
advanced
parental
age,
maternal
diabetes
during
pregnancy,
infections,
hormonal
imbalances,
certain
medications,
exposure
air
pollution.
Currently,
diagnosis
relies
on
behavioral
assessments,
but
the
absence
specific
molecular
biomarkers
poses
significant
obstacles
early
detection
targeted
therapies.
Encouragingly,
research
identified
potential
biomarkers,
such
neuroimaging
classifiers,
electroencephalography
patterns,
eye-tracking
data,
digital
analytics,
expression
profiles,
inflammatory
chemokine
markers,
proteomic
metabolomic
gut
microbiota
characteristics.
Potential
therapeutical
strategies
under
investigation
include
therapies,
non-invasive
brain
stimulation,
antioxidants,
oxytocin,
AVPR1a
antagonists,
PPAR
agonists,
mTOR
inhibitors.
This
review
explores
across
five
areas:
epidemiological
trends,
mechanisms,
their
roles,
diagnostic
therapeutic
approaches.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 19, 2025
ABSTRACT
Distal
1q21.1
deletions
and
duplications
are
associated
with
variable
phenotypes
including
autism,
head
circumference
height
defects.
To
elucidate
which
gene(s)
responsible
for
the
duplication/deletion-associated
phenotypes,
we
performed
gene
manipulation
in
zebrafish
mice.
We
modeled
duplication
by
overexpressing
eight
human
protein-coding
genes
zebrafish.
found
that
overexpression
of
CHD1L
only
led
to
macrocephaly
increased
larval
body
length,
whereas
chd1l
deletion
caused
opposite
phenotypes.
These
mirrored
were
also
observed
mouse
embryos.
Transcriptomic,
cistromic,
chromatin
accessibility
analyses
knock-out
hiPSC-derived
neuronal
progenitor
cells
revealed
regulates
expression
levels
involved
differentiation
synaptogenesis,
autism
genes.
Moreover,
favors
telencephalon
development
during
forebrain
regionalization
facilitating
pioneer
transcription
factors
SOX2
OTX2
while
simultaneously
compacting
through
its
interaction
repressor
NuRD
complex.
Last,
atypical
CNV
encompassing
pathogenic
missense
truncating
variants
individuals
autism.
Overall,
our
data
reveal
a
novel
role
as
master
regulator
cell
fate
dosage
imbalance
contributes
neuroanatomical
growth
distal
CNV.
GRAPHICAL
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 3, 2025
Abstract
Inborn
errors
of
immunity
(IEI),
formerly
known
as
primary
immune
deficiencies
(PID),
are
a
group
genetic
disorders
that
affect
the
system,
leading
to
increased
susceptibility
infections,
autoimmunity,
allergy,
and
cancer.
So
far,
449
IEI-causing
genes
have
been
identified
with
more
likely
be
discovered
rapid
adoption
whole
genome
sequencing
in
clinical
practice.
Patients
IEI
often
present
neurological
symptoms
such
cognitive
impairments,
neurodevelopmental
delay
even
seizures.
These
features
could
indicative
an
risk
(NDDs)
patient
population.
However,
date,
no
exhaustive
study
has
done
on
overlap
between
NDDs
IEIs.
Using
publicly
available
NDD
variant
databases,
gene
ontology
analysis,
machine
learning,
protein-network
clustering
we
found
one-third
were
also
linked
NDDs.
primarily
involved
development
DNA
repair
pathways.
In
contrast,
causing
exclusively
IEIs
enriched
response
functions.
Functional
connectivity
analysis
revealed
NDD-risk
integrated
immune-related
networks,
including
those
repair,
highlighting
immune-NDD
interactions.
Altogether,
this
work
demonstrates
molecular
level
genes.
Our
strongly
suggests
phenotypes
patients
underreported
NDD-related
databases.
Abstract
Genetic
risk
for
psychiatric
disorders
lies
largely
within
non-coding
regions,
where
the
lack
of
detailed
knowledge
gene
regulation
and
chromatin
structure
has
hampered
understanding
disease
mechanisms.
We
analyzed
accessibility
3D
genome
architecture
in
brains
from
53
ASD
neurotypical
individuals,
including
patients
with
(dup)
15q11-13.
observed
reduced
CTCF
binding,
which
had
dual
effects:
a)
decreased
at
distal
enhancers
downregulation
synaptic
neuronal
target
genes,
b)
weakened
TAD
boundaries
linked
to
DNA
hypermethylation,
impacting
a
distinct
set
genes.
These
changes
were
associated
brain
mQTLs,
caQTLs,
rare
variants
increasing
risk,
subset
we
validated
by
CRISPR
editing,
supporting
causal
relationship.
Our
analyses
suggest
that
genetic
contribute
part
through
combination
epigenetic
changes,
disruption
enhancer
organization
both
idiopathic
syndromic
form
ASD.
Asian Journal of Psychiatry,
Год журнала:
2025,
Номер
unknown, С. 104501 - 104501
Опубликована: Апрель 1, 2025
Alternative
splicing
(AS)
is
a
vital
and
highly
dynamic
RNA
regulatory
mechanism
that
allows
single
gene
to
generate
multiple
mRNA
protein
isoforms.
Dysregulation
of
AS
has
been
identified
as
key
contributor
the
pathogenesis
autism
spectrum
disorders
(ASD).
A
comprehensive
understanding
aberrant
mechanisms
their
functional
consequences
in
ASD
can
help
uncover
molecular
basis
disorder
facilitate
development
therapeutic
strategies.
This
review
focuses
on
major
events
regulators
associated
with
ASD,
highlighting
roles
linking
defective
pathogenesis.
In
addition,
discussion
how
emerging
technologies,
such
long-read
sequencing,
single-cell
spatial
transcriptomics
CRISPR-Cas
systems
are
offering
novel
insights
into
role
presented.
Finally,
splicing-based
strategies
evaluated,
emphasizing
potential
address
unmet
clinical
needs
treatment.
