medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 26, 2024
ABSTRACT
Background
Clinical
genetic
evaluation
of
dilated
cardiomyopathy
(DCM)
is
implemented
variably
or
not
at
all.
Identifying
needs
and
barriers
to
evaluations
will
enable
strategies
enhance
precision
medicine
care.
Methods
An
online
survey
was
conducted
in
June
2024
among
cardiologist
investigators
the
DCM
Consortium
from
US
advanced
heart
failure/transplant
(HF/TX)
programs
collect
demographics,
training,
program
characteristics,
practices
for
DCM,
implementation
needs.
in-person
discussion
followed.
Results
Twenty-five
cardiologists
(28%
female,
12%
Hispanic,
68%
White)
participated
15
discussion;
genetics
training
backgrounds
varied
greatly.
testing
by
all
with
annual
uptake
ranging
5%-70%
(median
25%).
Thirteen
respondents
(52%)
did
use
selection
criteria
whereas
others
selected
patients
based
on
specific
clinical
family
history
data.
Eight
(32%)
ordered
themselves,
remainder
had
managed
mostly
a
counselor
expertise
(16/17;
94%).
Six
themes
were
distilled
open-ended
responses
regarding
thoughts
future
included
access
services,
navigating
uncertainty,
knowledge
needs,
cost
concerns,
family-based
care
barriers,
institutional
infrastructure
limitations.
Following
an
discussion,
four
areas
identified
focused
effort:
improved
reimbursement
integration
HF/TX
teams,
provider
education
resources,
more
research
find
missing
heritability
resolve
uncertain
results.
Conclusions
have
challenges
provision
evaluations;
targeted
plans
facilitate
are
needed.
Pediatric Research,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 8, 2025
Abstract
Cardiomyopathy
in
children
is
a
leading
cause
of
heart
failure
and
cardiac
transplantation.
Disease-associated
genetic
variants
play
significant
role
the
development
different
subtypes
disease.
Genetic
testing
increasingly
being
recognized
as
standard
care
for
diagnosing
this
heterogeneous
group
disorders,
guiding
management,
providing
prognostic
information,
facilitating
family-based
risk
stratification.
The
increase
clinical
research
within
field
has
led
to
new
insights
into
disorders.
Mutations
genes
encoding
sarcomere,
cytoskeletal,
Z-disk,
sarcolemma
proteins
appear
major
causing
overlapping
phenotypes
called
cardioskeletal
myopathies
through
“final
common
pathway”
links.
For
myocarditis,
high
frequency
infectious
exposures
wide
spectrum
presentation
suggest
that
factors
mediate
course
disease,
including
alleles,
an
association
with
cardiomyopathy,
undiagnosed
arrhythmogenic
cardiomyopathy.
Finally,
while
we
have
made
strides
elucidating
architecture
pediatric
understanding
implications
uncertain
significance
remains
issue.
need
continued
innovation
great,
particularly
basis
drive
forward
targeted
precision
medicine
gene
therapy
efforts.
Impact
skeletal
myopathy
can
occur
same
patient
secondary
mutations
encode
sarcomeric
or
cytoskeletal
proteins,
which
are
expressed
both
muscle
groups,
highlighting
there
final
pathways
myocarditis
likely
complex
interaction
multiple
environmental
factors,
suggesting
utility
patients
those
higher
groups.
Given
prevalence
testing,
better
bioinformatic
tools
pipelines
needed
resolve
their
meaning.
Frontiers in Cardiovascular Medicine,
Год журнала:
2024,
Номер
11
Опубликована: Июнь 13, 2024
This
case
report
details
the
identification
of
a
novel
likely
pathogenic
splicing
variant
in
TTN
gene,
associated
with
dilated
cardiomyopathy
(DCM),
42-year-old
male
patient
presenting
early-onset
heart
failure
and
reduced
ejection
fraction.
DCM
is
nonischemic
condition
characterized
by
left
biventricular
dilation
systolic
dysfunction,
approximately
one-third
cases
being
familial
often
linked
to
genetic
mutations.
The
encoding
largest
human
protein
essential
for
muscle
contraction
sarcomere
structure,
implicated
about
25%
through
mutations,
especially
truncating
variants.
Our
investigation
revealed
previously
unreported
G
>
C
mutation
at
splice
acceptor
site
intron
356
TTN,
confirmed
Sanger
sequencing
not
found
population
databases,
suggesting
contribution
understanding
etiology.
emphasizes
critical
role
gene
cardiac
function
complexity
underlying
DCM.
A
comprehensive
literature
review
highlighted
prevalence
significance
variants
particularly
those
affecting
titin
A-band,
which
known
its
stability.
variant's
underscores
importance
screening
patients
DCM,
offering
insights
into
disease's
transmission
potential
therapeutic
targets.
findings
contribute
expanding
knowledge
factors
demonstrating
necessity
integrating
diagnostics
cardiovascular
medicine.
supports
growing
evidence
linking
mutations
specific
regions
development
counseling
testing
managing
disease.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(7), С. 3807 - 3807
Опубликована: Март 29, 2024
Dilated
cardiomyopathy
is
a
heterogeneous
entity
that
leads
to
heart
failure
and
malignant
arrhythmias.
Nearly
50%
of
cases
are
inherited;
therefore,
genetic
analysis
crucial
unravel
the
cause
for
early
identification
carriers
at
risk.
A
large
number
variants
remain
classified
as
ambiguous,
impeding
an
actionable
clinical
translation.
Our
goal
was
perform
comprehensive
update
previously
with
ambiguous
role,
applying
new
algorithm
already
available
tools.
In
cohort
65
diagnosed
dilated
cardiomyopathy,
total
125
were
ambiguous.
reanalysis
resulted
in
reclassification
12%
from
unknown
likely
benign
or
pathogenic
due
improved
population
frequencies.
For
all
remaining
variants,
we
used
our
algorithm;
60.9%
showed
potential
but
not
confirmed
deleterious
24.5%
role.
Periodically
updating
frequencies
cheap
fast
action,
making
it
possible
clarify
role
variants.
Here,
help
most
specific
algorithms
facilitate
interpretation
cardiomyopathy.
