Genes,
Год журнала:
2025,
Номер
16(1), С. 104 - 104
Опубликована: Янв. 19, 2025
Mendelian
disorders
of
the
epigenetic
machinery
(MDEMs)
include
a
large
number
conditions
caused
by
defective
activity
member
machinery.
MDEMs
are
characterized
multiple
congenital
abnormalities,
intellectual
disability
and
abnormal
growth.
that
can
be
variably
up-
or
down-regulated.
Background/Objectives:
In
several
MDEMs,
predisposition
to
metabolic
syndrome
obesity
since
childhood
has
been
reported.
Methods:
To
investigate
bases
this
growth,
we
collected
physical
data
from
heterogeneous
pool
38
patients
affected
MDEMs.
Thirty-five
performed
indirect
calorimetry
(as
measure
resting
energy
expenditure,
REE)
blood
tests
monitor
plasmatic
nutritional
parameters.
Conclusions:
Although
limited
small-sized
sample,
our
study
demonstrates
linear
correlation
between
REE
parameters,
OFC,
height
weight,
observed
slight
imbalance
on
spies
predisposition.
Furthermore,
demonstrated
significantly
higher
in
Sotos
Syndrome
type
1
compared
controls,
which
resulted
independent
height,
suggesting
impaired
metabolism
these
may
go
beyond
overgrowth.
Epigenetics & Chromatin,
Год журнала:
2025,
Номер
18(1)
Опубликована: Фев. 1, 2025
Epigenes
are
defined
as
proteins
that
perform
post-translational
modification
of
histones
or
DNA,
reading
modifications,
form
complexes
with
epigenetic
factors
changing
the
general
structure
chromatin.
This
specialized
group
is
responsible
for
controlling
organization
genomic
DNA
in
a
cell-type
specific
fashion,
normal
development
spatial
and
temporal
fashion.
Moreover,
mutations
epigenes
have
been
implicated
causal
germline
pediatric
disorders
driver
cancer.
Despite
their
importance
to
human
disease,
date,
there
has
not
systematic
analysis
sources
functional
diversity
at
large.
Epigenes'
unique
functions
require
assembly
pools
within
nucleus
suggest
amino
acid
composition
would
enriched
features
enable
efficient
chromatin
transcription,
splicing,
modifications.
In
this
study,
we
assess
stemming
from
gene
structure,
isoforms,
protein
domains,
multiprotein
complex
formation
drive
established
epigenes.
We
found
structural
variable
roles
depending
on
cellular
environmental
context.
First,
significantly
larger
more
exons
compared
non-epigenes
which
contributes
increased
isoform
diversity.
Second
participate
multimeric
than
non-epigenes.
Thirdly,
given
proposed
membraneless
organelles,
show
substantially
intrinsically
disordered
regions
(IDRs).
Additionally,
assessed
specificity
expression
profiles
showed
ubiquitously
expressed
consistent
enrichment
syndromes
intellectual
disability,
multiorgan
dysfunction,
developmental
delay.
Finally,
L1000
dataset,
identify
drugs
can
potentially
be
used
modulate
these
genes.
Here
significant
differences
usage,
domain
content,
binding
partners
between
using
various
genomics
datasets
Ensembl,
ENCODE,
GTEx,
HPO,
LINCS
L1000,
BrainSpan.
Our
results
contribute
new
knowledge
growing
field
focused
developing
targeted
therapies
diseases
caused
by
epigene
mutations,
such
chromatinopathies
cancers.
Journal of Applied Genetics,
Год журнала:
2024,
Номер
65(2), С. 287 - 301
Опубликована: Янв. 5, 2024
Abstract
Chromatinopathies
(CPs),
a
group
of
rare
inborn
defects
characterized
by
chromatin
state
imbalance,
have
evolved
from
initially
resembling
Cornelia
de
Lange
syndrome
to
encompass
wide
array
genetic
diseases
with
diverse
clinical
presentations.
The
CPs
classification
now
includes
human
developmental
disorders
caused
germline
mutations
in
epigenes,
genes
that
regulate
the
epigenome.
Recent
advances
next-generation
sequencing
enabled
association
154
epigenes
CPs,
revealing
distinctive
DNA
methylation
patterns
known
as
episignatures.
It
has
been
shown
episignatures
are
unique
for
particular
CP
or
share
similarities
among
specific
subgroup.
Consequently,
these
emerged
promising
biomarkers
diagnosing
and
treating
differentiating
subtypes,
evaluating
variants
unknown
significance,
facilitating
targeted
therapies
tailored
underlying
epigenetic
dysregulation.
following
review
was
conducted
collect,
summarize,
analyze
data
regarding
such
aspects
evaluation
encompassing
long-term
patient
care,
changes,
innovative
molecular
bioinformatic
methodologies
devised
assessment
CPs.
We
also
shed
light
on
novel
treatment
options
surfaced
recent
research
presented
synthesis
ongoing
trials,
contributing
current
understanding
dynamic
evolving
nature
investigation.
Molecular Genetics and Metabolism,
Год журнала:
2024,
Номер
142(1), С. 108360 - 108360
Опубликована: Фев. 27, 2024
The
Mendelian
disorders
of
chromatin
machinery
(MDCMs)
represent
a
distinct
subgroup
that
present
with
neurodevelopmental
disability.
regulates
gene
expression
by
range
mechanisms,
including
post-translational
modification
histones,
responding
to
histone
marks,
and
remodelling
nucleosomes.
Some
the
MDCMs
impact
on
may
have
potential
therapeutic
interventions.
Two
treatment
strategies
are
enhance
intracellular
pool
metabolites
can
act
as
substrates
for
modifiers
use
medications
inhibit
or
promote
residues
influence
expression.
In
this
article
we
discuss
treatments
modifications
involving
acetylation
methylation.
Genomic
technologies
facilitating
earlier
diagnosis
many
disorders,
providing
opportunities
early
from
infancy.
This
has
parallels
how
inborn
errors
metabolism
been
afforded
newborn
screening.
Before
promise
be
fulfilled,
require
greater
understanding
biochemical
fingerprint
these
conditions,
which
provide
supplement
modifying
enzymes.
Importantly,
metabolomic
profile
affected
individuals
also
disorder-specific
biomarkers
will
critical
demonstrating
efficacy
treatment,
response
not
able
accurately
assessed
clinical
measures.
BMC Medical Genomics,
Год журнала:
2024,
Номер
17(1)
Опубликована: Ноя. 29, 2024
Abstract
Background
Rare
variants
in
epigenes
(a.k.a.
chromatin
modifiers),
a
class
of
genes
that
control
epigenetic
regulation,
are
commonly
identified
both
pediatric
neurodevelopmental
syndromes
and
as
somatic
cancer.
However,
little
is
known
about
the
extent
shared
disruption
signaling
pathways
by
same
epigene
across
different
diseases.
To
address
this,
we
study
an
epigene,
Additional
Sex
Combs-like
1
(
ASXL1
),
where
truncating
heterozygous
cause
Bohring-Opitz
syndrome
(BOS,
OMIM
#605039),
germline
disorder,
while
driver
events
acute
myeloid
leukemia
(AML).
No
BOS
patients
have
been
reported
to
AML.
Methods
This
explores
common
dysregulated
with
We
analyzed
whole
blood
transcriptomic
DNA
methylation
data
from
AML
-variant
(AML-
)
examined
differential
exon
usage
cell
proportions.
Results
Our
analyses
molecular
signatures
between
AML-
highlighted
key
biomarkers,
including
VANGL2
,
GRIK5
GREM2
samples
variants,
regardless
disease
type.
Notably,
our
revealed
significant
de-repression
posterior
homeobox
A
HOXA
upregulation
Wnt-signaling
hematopoietic
regulator
HOXB4
.
While
discovered
many
features,
also
splice
isoforms
RUNX3
long
isoform,
p46,
preferentially
expressed
BOS,
shorter
p44
isoform
ASXL1.
Conclusion
findings
highlight
strong
effects
supersede
cell-type
even
states.
first
direct
comparison
profiles
driven
pathogenic
modifier
gene
distinct
Similar
RASopathies,
which
lead
overlapping
phenotypes
can
be
treated
inhibiting
pathway,
identifies
for
targeted
Comparative
approaches
high-penetrance
genetic
types
states
identify
targetable
treat
multiple
Finally,
work
highlights
connections
epigenes,
such
underlying
stem-cell
state
early
development
malignancy.
ACS Measurement Science Au,
Год журнала:
2024,
Номер
4(3), С. 247 - 259
Опубликована: Фев. 22, 2024
Precision
medicine
is
a
new
medical
approach
which
considers
both
population
characteristics
and
individual
variability
to
provide
customized
healthcare.
The
transition
from
traditional
reactive
personalized
based
on
biomarker-driven
process
deep
knowledge
of
biological
mechanisms
according
the
development
diseases
occurs.
In
this
context,
advancements
in
high-throughput
omics
technologies
represent
unique
opportunity
discover
novel
biomarkers
an
unbiased
picture
system.
One
fields
science
has
started
be
recently
applied
that
ophthalmology.
Ocular
are
very
common,
some
them
could
highly
disabling,
thus
leading
vision
loss
blindness.
pathogenic
mechanism
most
ocular
may
dependent
various
genetic
environmental
factors,
whose
effect
not
been
yet
completely
understood.
large-scale
approaches
fundamental
have
comprehensive
evaluation
whole
system
essential
tool
for
therapies.
This
Review
summarizes
recent
ophthalmology
last
ten
years,
particular
by
focusing
proteomics,
metabolomics
lipidomics
applications
analytical
perspective.
role
high-efficiency
separation
techniques
coupled
(high-resolution)
mass
spectrometry
((HR)MS)
also
discussed,
as
well
impact
sampling,
sample
preparation
data
analysis
integrating
parts
workflow.
médecine/sciences,
Год журнала:
2024,
Номер
40(12), С. 914 - 924
Опубликована: Дек. 1, 2024
Le
développement
des
technologies
de
séquençage
et
leur
accessibilité
accrue
dans
les
services
hospitaliers
laboratoires
génétique
a
considérablement
accéléré
l’identification
variants
génétiques
associés
aux
maladies
rares.
Parmi
celles-ci,
la
machinerie
épigénétique
(MGME)
se
caractérisent
par
présence
mutations
gènes
codant
régulateurs
épigénétiques
qui
jouent
un
rôle
clé
le
l’organisme
fonctions
cellulaires.
En
conséquence,
perte
fonction
ces
entraînerait
modifications
l’épigénome
affectant
profondément
l’expression
du
génome
l’identité
cellulaire.
À
ce
titre,
perturbations
profil
méthylation
l’ADN
ont
été
décrites
plusieurs
MGME
constituent
d’ores
déjà
outil
reconnu
d’aide
au
diagnostic.
L’enjeu
est
maintenant
savoir
si
comment
altérations
sont
à
l’origine
manifestations
cliniques
chez
patients
atteints
cette
classe
particulière
monogéniques.
Ainsi,
l’étude
peut
nous
éclairer
sur
l’importance
l’épigénétique
en
santé,
notamment
mécanismes
impliqués
l’émergence
compréhension
complexes
comme
neurodéveloppementales
ou
cancers.
Human Genetics,
Год журнала:
2023,
Номер
142(12), С. 1705 - 1720
Опубликована: Окт. 20, 2023
Abstract
Arboleda-Tham
Syndrome
(ARTHS)
is
a
rare
genetic
disorder
caused
by
heterozygous,
de
novo
mutations
in
Lysine(K)
acetyltransferase
6A
(
KAT6A)
.
ARTHS
clinically
heterogeneous
and
characterized
several
common
features,
including
intellectual
disability,
developmental
speech
delay,
hypotonia,
affects
multiple
organ
systems.
KAT6A
the
enzymatic
core
of
histone–acetylation
protein
complex;
however,
direct
histone
targets
gene
regulatory
effects
remain
unknown.
In
this
study,
we
use
patient
n
=
8)
control
14)
dermal
fibroblasts
perform
comprehensive
profiling
epigenome
transcriptome
mutations.
We
identified
differential
chromatin
accessibility
within
promoter
or
body
23%
(14/60)
genes
that
were
differentially
expressed
between
controls.
Within
fibroblasts,
show
distinct
set
from
posterior
HOXC
cluster
HOXC10
,
HOXC11
HOXC-AS3
HOXC-AS2
HOTAIR
)
are
overexpressed
transcription
factors
critical
for
early
development
segment
patterning.
The
genomic
loci
harboring
epigenetically
regulated
with
increased
accessibility,
high
levels
H3K23ac,
gene–body
DNA
methylation
compared
to
controls,
all
which
consistent
transcriptomic
overexpression.
Finally,
used
unbiased
proteomic
mass
spectrometry
two
new
post-translational
modifications
(PTMs)
disrupted
ARTHS:
H2A
H3K56
acetylation.
Our
multi-omics
assays
have
novel
roles
large
group
patients
diverse
pathogenic
This
work
provides
insight
into
role
on
epigenomic
regulation
somatic
cell
types.
We
demonstrate
an
early-stage
prototype
of
image-guided
laser
ablation
system
for
precise
3D
sampling
fresh-frozen
tissue
samples
subsequent
analysis
biomolecules.
Utilizing
integrated
reflected
light
microscope
and
optical
coherence
tomography,
pre-recorded
image
data
(e.g.
characterized
slices)
can
be
registered
mapped
to
the
coordinate
aiming
ablation.
With
this
system,
we
are
analyzing
a
variety
from
our
many
collaborators
at
University
Cancer
Center
Hamburg
(UCCH)
cancer
research
system's
feasibility
through
initial
use
cases.
