Birth Defects Research,
Год журнала:
2024,
Номер
116(7)
Опубликована: Июль 1, 2024
Abstract
Background
Chromatinopathies
are
a
heterogeneous
group
of
genetic
disorders
caused
by
pathogenic
variants
in
genes
coding
for
chromatin
state
balance
proteins.
Remarkably,
many
these
syndromes
present
unbalanced
postnatal
growth,
both
under‐
and
over‐,
although
little
has
been
described
the
literature.
Fetal
growth
measurements
common
practice
pregnancy
management
values
within
normal
ranges
indicate
proper
intrauterine
progression;
on
contrary,
abnormalities
fetal
open
discussion
possible
pathogenesis
affecting
even
period.
Methods
Among
numerous
chromatinopathies,
we
have
selected
six
most
documented
literature
offering
evidence
about
two
overgrowth
(Sotos
Weaver
syndrome)
four
undergrowth
(Bohring
Opitz,
Cornelia
de
Lange,
Floating‐Harbor,
Meier
Gorlin
syndrome),
describing
their
molecular
characteristics,
maternal
biochemical
results
early
findings,
prenatal
ultrasound
characteristics.
Results/Conclusion
To
date,
scarce
data
findings
few
inconclusive,
though
parameters
may
contribute
to
more
rapid
accurate
diagnosis,
calling
better
detailed
description
findings.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 2, 2024
The
link
between
DNA
methylation
and
neurodevelopmental
disorders
is
well
established.
However,
how
fine-tuned—ensuring
precise
gene
expression
developmental
fidelity—remains
poorly
understood.
PROSER1,
a
known
TET2
interactor,
was
recently
linked
to
severe
disorder.
Here,
we
demonstrate
that
PROSER1
interacts
with
all
TET
enzymes
stabilizes
chromatin-bound
TET-OGT-PROSER1-DBHS
(TOPD)
complexes,
which
regulate
demethylation
expression.
Surprisingly,
find
also
sequesters
enzymes,
preventing
widespread
transposable
element
de-repression.
Our
findings
identify
as
key
factor
both
positively
negatively
regulates
essential
for
mammalian
neurodevelopment.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июнь 18, 2023
Abstract
Arboleda-Tham
Syndrome
(ARTHS,
OMIM#616268)
is
a
rare
neurodevelopmental
disorder
caused
by
de
novo
mutations
in
KAT6A
.
Individuals
with
ARTHS
typically
exhibit
varying
degrees
of
intellectual
disability,
speech
and
language
deficits
clinical
manifestations
across
multiple
systems
that
lead
to
abnormal:
vision,
craniofacial
features,
cardiac
morphology,
gastrointestinal
function.
To
gain
insight
into
the
potential
neuropathological
mechanisms
underlying
ARTHS,
we
investigate
how
disrupt
vitro
brain
development
using
induced
pluripotent
stem
cells
(iPSCs)
cerebral
organoids
(COs)
derived
from
patients
harboring
nonsense
mutations.
In
this
study,
conducted
comprehensive
transcriptomic
profiling
performing
time-course
experiments
generating
short-read
long-read
RNA
sequencing
(RNA-seq)
data
undifferentiated
iPSCs
COs
at
15
25
days
neural
differentiation.
Our
analysis
revealed
abnormal
expression
235
genes
all
three
timepoints
examined.
Notably,
observed
persistent
dysregulation
such
as
CTSF
,
ZNF229
PCDHB12
PAK3
Additionally,
found
consistent
enrichment
PTBP1
-target
among
upregulated
stages
assessed
RNA-seq.
During
differentiation,
identified
980
consistently
display
aberrant
transcription
both
CO
stages.
These
are
enriched
for
involved
cell
fate
determination
through
modulation
cell-cycle
dynamics
(e.g.
E2F
family)
cell-adhesion
molecules
PCDH
genes).
findings
indicate
slower
downregulation
pluripotency
cycle
compared
controls
delay
led
an
overrepresentation
cycling
human
progenitor
markers
during
differentiation
ARTHS.
Finally,
matching
variable
neurodevelopment
phenotypes
discovered
aberrantly
expressed
associated
Autism
Spectrum
Disorder
Epilepsy,
subset
showing
isoform-specific
dysregulation.
Strikingly,
same
PTBP1-
target
were
amongst
differential
isoform
usage
For
first
time,
demonstrate
repressing
suggesting
prolonged
activation
these
gene
networks
disrupts
temporal
