bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 14, 2024
Abstract
Autism
Spectrum
Disorder
(ASD)
is
a
highly
heritable
condition
with
diverse
clinical
presentations.
Approximately
20%
of
ASD’s
genetic
susceptibility
imparted
by
de
novo
mutations
major
effect,
most
which
cause
haploinsufficiency.
We
mapped
enhancers
two
high
confidence
autism
genes
–
CHD8
and
SCN2A
used
CRISPR-based
gene
activation
(CRISPR-A)
in
hPSC-derived
excitatory
neurons
cerebral
forebrain
organoids
to
correct
the
effects
haploinsufficiency,
taking
advantage
presence
wildtype
allele
each
endogenous
regulation.
found
that
CRISPR-A
induced
sustained
increase
expression
treated
organoids,
rescue
levels
mutation-associated
phenotypes,
including
physiology.
These
data
support
via
targeting
haploinsufficient
genes,
as
therapeutic
intervention
ASD
other
neurodevelopmental
disorders.
BMJ Open,
Journal Year:
2024,
Volume and Issue:
14(6), P. e080746 - e080746
Published: June 1, 2024
Autism
is
a
common
neurodevelopmental
condition
with
complex
genetic
aetiology
that
includes
contributions
from
monogenic
and
polygenic
factors.
Many
autistic
people
have
unmet
healthcare
needs
could
be
served
by
genomics-informed
research
clinical
trials.
The
primary
aim
of
the
European
GEnomics
Registry
(EAGER)
to
establish
registry
participants
diagnosis
autism
or
an
associated
rare
who
undergone
whole-genome
sequencing.
can
facilitate
recruitment
for
future
trials
studies,
based
on
genetic,
phenotypic
profiles,
as
well
participant
preferences.
secondary
EAGER
investigate
association
between
mental
physical
health
characteristics
participants'
profiles.
Journal of Autism and Developmental Disorders,
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 11, 2023
A
considerable
number
of
screening
and
diagnostic
tools
for
autism
exist,
but
variability
in
these
measures
presents
challenges
to
data
harmonization
the
comparability
generalizability
findings.
At
same
time,
there
is
a
movement
away
from
symptomatology
stances
that
capture
heterogeneity
appreciate
diversity.
The
International
Classification
Functioning,
Disability
Health
(ICF)
provides
classification
system
can
support
content
different
while
enabling
translation
information
into
functioning.Here
we
linked
commonly
used
within
field
ICF
facilitate
unification
obtained
measures.As
expected,
primarily
focus
on
body
functions
activities
participation
domains
ICF,
much
less
environmental
factors,
reflecting
biomedical
adaptive
behavior
operationalizations
derived
manuals.By
translating
symptomology-based
continuous
diagnostically
neutral
view
functioning,
linking
presented
here
may
provide
means
harmonize
characteristics
be
re-examined
through
more
neurodiversity-affirmative
lens.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 14, 2024
Abstract
Autism
Spectrum
Disorder
(ASD)
is
a
highly
heritable
condition
with
diverse
clinical
presentations.
Approximately
20%
of
ASD’s
genetic
susceptibility
imparted
by
de
novo
mutations
major
effect,
most
which
cause
haploinsufficiency.
We
mapped
enhancers
two
high
confidence
autism
genes
–
CHD8
and
SCN2A
used
CRISPR-based
gene
activation
(CRISPR-A)
in
hPSC-derived
excitatory
neurons
cerebral
forebrain
organoids
to
correct
the
effects
haploinsufficiency,
taking
advantage
presence
wildtype
allele
each
endogenous
regulation.
found
that
CRISPR-A
induced
sustained
increase
expression
treated
organoids,
rescue
levels
mutation-associated
phenotypes,
including
physiology.
These
data
support
via
targeting
haploinsufficient
genes,
as
therapeutic
intervention
ASD
other
neurodevelopmental
disorders.
