Medical Review,
Journal Year:
2024,
Volume and Issue:
5(2), P. 139 - 151
Published: Sept. 2, 2024
Neurodevelopmental
disorders
(NDDs)
are
a
group
of
highly
heterogeneous
diseases
that
affect
children's
social,
cognitive,
and
emotional
functioning.
The
etiology
is
complicated
with
genetic
factors
playing
an
important
role.
During
the
past
decade,
large-scale
whole
exome
sequencing
(WES)
genome
(WGS)
have
vastly
advanced
findings
NDDs.
Various
forms
variants
been
reported
to
contribute
NDDs,
such
as
de
novo
mutations
(DNMs),
copy
number
variations
(CNVs),
rare
inherited
(RIVs),
common
variation.
By
far,
over
200
high-risk
NDD
genes
identified,
which
involved
in
biological
processes
including
synaptic
function,
transcriptional
epigenetic
regulation.
In
addition,
monogenic,
oligogenic,
polygenetic,
omnigenic
models
proposed
explain
architecture
However,
majority
patients
still
do
not
definitive
diagnosis.
future,
more
types
risk
factors,
well
noncoding
variants,
await
be
their
interplay
mechanisms
key
resolving
heterogeneity
Nature Medicine,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 17, 2025
Genetic
diagnosis
of
rare
diseases
requires
accurate
identification
and
interpretation
genomic
variants.
Clinical
molecular
scientists
from
37
expert
centers
across
Europe
created
the
Solve-Rare
Diseases
Consortium
(Solve-RD)
resource,
encompassing
clinical,
pedigree
rare-disease
data
(94.5%
exomes,
5.5%
genomes),
performed
systematic
reanalysis
for
6,447
individuals
(3,592
male,
2,855
female)
with
previously
undiagnosed
6,004
families.
We
established
a
collaborative,
two-level
review
infrastructure
that
allowed
genetic
in
506
(8.4%)
Of
552
disease-causing
variants
identified,
464
(84.1%)
were
single-nucleotide
or
short
insertions/deletions.
These
either
located
recently
published
novel
disease
genes
(n
=
67),
reclassified
ClinVar
187)
by
consensus
decision
within
Solve-RD
210).
Bespoke
bioinformatics
analyses
identified
remaining
15.9%
causative
88).
Ad
hoc
review,
parallel
to
reanalysis,
diagnosed
249
(4.1%)
additional
families
an
overall
diagnostic
yield
12.6%.
The
collaborative
networks
set
up
can
serve
as
blueprint
future
further
scalable
international
efforts.
resource
is
open
global
community,
allowing
phenotype,
variant
gene
queries,
well
genome-wide
discoveries.
Journal of Translational Medicine,
Journal Year:
2025,
Volume and Issue:
23(1)
Published: March 6, 2025
Gastric
cancer
(GC)
is
one
of
the
most
common
malignancies.
Previous
studies
have
shown
that
mitochondrial
metabolism
associated
with
However,
relevant
research
on
mitochondria-related
lncRNAs
in
GC
lacking.
We
integrated
corresponding
information
patients
from
The
Cancer
Genome
Atlas
(TCGA)
database.
Mitochondria-related
were
selected
based
differential
expression
and
a
correlation
analysis
to
construct
prognostic
model.
mutation
data
analyzed
distinguish
differences
tumor
burden
(TMB).
Single-sample
gene
set
enrichment
(ssGSEA)
was
performed
evaluate
immunological
differences.
A
series
cell-based
experiments
adopted
biological
behavior
GC.
total
1571
identified.
signature
incorporating
nine
built
293
suitable
cases
could
predict
patient
prognosis.
TMB
ssGSEA
indicated
low-risk
group
displayed
increased
immune
function.
differentially
expressed
genes
enriched
metabolic
functions.
AC129507.1
significantly
upregulated
cells
poor
prognosis,
its
knockdown
inhibited
proliferation
migration
cells.
Mechanistically,
silencing
led
abnormal
glycolipid
oxidative
stress,
thus
inducing
ferroptosis.
Our
nine-lncRNA
risk
powerfully
promoted
malignant
phenotypes
play
nonnegligible
role
by
promoting
formation
immunosuppressive
microenvironment
inhibiting
initiation
ferroptosis,
which
needs
be
further
explored.
medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 6, 2025
The
U4
small
nuclear
RNA
(snRNA)
forms
a
duplex
with
the
U6
snRNA
and,
together
U5
and
∼30
proteins,
is
part
of
U4/U6.U5
tri-snRNP
complex,
located
at
core
major
spliceosome.
Recently,
recurrent
de
novo
variants
in
RNA,
transcribed
from
RNU4-2
gene,
least
two
other
RNU
genes
were
discovered
to
cause
neurodevelopmental
disorder.
We
detected
inherited
heterozygous
(n.18_19insA
n.56T>C)
four
out
five
RNU6
paralogues
(n.55_56insG
n.56_57insG)
135
individuals
62
families
non-syndromic
retinitis
pigmentosa
(RP),
rare
form
hereditary
blindness.
show
that
these
are
among
RP
invariably
cluster
close
proximity
within
three-way
junction
(between
stem-I,
5'
stem-loop
stem-II)
U4/U6
duplex,
affecting
its
natural
conformation.
Interestingly,
this
region
binds
numerous
splicing
factors
complex
including
PRPF3,
PRPF8
PRPF31,
previously
associated
as
well.
identified
seem
affect
snRNP
biogenesis,
namely
di-snRNP,
which
an
assembly
intermediate
tri-snRNP.
Based
on
number
positive
cases
observed,
deleterious
could
be
significant
isolated
or
dominant
RP,
accounting
for
up
1.2%
all
undiagnosed
cases.
This
study
highlights
role
non-coding
Mendelian
disorders
uncovers
pleiotropy
,
where
different
underlie
disorder
RP.
Open Biology,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: Jan. 1, 2025
The
established
consensus
sequence
for
human
5′
splice
sites
masks
the
presence
of
two
major
site
classes
defined
by
preferential
base-pairing
potentials
with
either
U5
snRNA
loop
1
or
U6
ACAGA
box.
are
separable
in
genome
sequences,
sensitized
specific
genotypes
and
associated
splicing
complexity.
reflect
commitment
to
usage
occurring
primarily
during
transfer
snRNA.
Separating
into
its
constituents
can
help
us
understand
fundamental
features
eukaryote
architecture
mechanisms
inform
treatment
design
diseases
caused
genetic
variation
affecting
splicing.
