Frontiers in Endocrinology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 18, 2025
Endocrine
system
disorders
are
a
serious
public
health
burden
and
can
be
caused
by
deleterious
genetic
variants
in
single
genes
or
the
combined
effects
of
multiple
along
with
environmental
lifestyle
factors.
The
EndoGene
database
presents
results
next-generation
sequencing
assays
used
to
genetically
profile
5,926
patients
who
were
diagnosed
450
endocrine
concomitant
diseases
examined
treated
at
National
Medical
Research
Center
for
Endocrinology
between
November
2017
January
2024.
Among
them,
494,
1,785,
692,
1,941
profiled
using
four
internally
developed
panels
including
220,
250,
376,
382
genes,
respectively,
selected
based
on
literature
analysis
clinical
recommendations,
1,245
whole
exome
covering
31,969
genes.
2,711
reported
as
clinically
relevant
medical
geneticists
presented
here
genomic,
technical,
annotations.
This
publicly
accessible
will
useful
those
interested
genetics,
epidemiology,
population
statistics,
better
understanding
molecular
basis
disorders.
Journal of the Endocrine Society,
Год журнала:
2019,
Номер
3(8), С. 1545 - 1573
Опубликована: Июнь 14, 2019
Abstract
Polycystic
ovary
syndrome
(PCOS)
is
a
heterogeneous
disorder
characterized
by
hyperandrogenism
and
chronic
anovulation.
Depending
on
diagnostic
criteria,
6%
to
20%
of
reproductive
aged
women
are
affected.
Symptoms
PCOS
arise
during
the
early
pubertal
years.
Both
normal
female
development
irregular
menstrual
cycles,
anovulation,
acne.
Owing
complicated
interwoven
pathophysiology,
discerning
inciting
causes
challenging.
Most
available
clinical
data
communicate
findings
outcomes
in
adult
women.
Whereas
Rotterdam
criteria
accepted
for
women,
different
adolescent
girls
have
been
delineated.
Diagnostic
features
irregularity,
hyperandrogenism,
and/or
hyperandrogenemia.
Pelvic
ultrasound
not
needed
diagnosis
girls.
Even
before
definitive
PCOS,
adolescents
with
signs
androgen
excess
oligomenorrhea/amenorrhea,
can
be
regarded
as
being
“at
risk
PCOS.”
Management
both
those
at
confirmed
includes
education,
healthy
lifestyle
interventions,
therapeutic
interventions
targeting
their
symptoms.
Interventions
include
metformin,
combined
oral
contraceptive
pills,
spironolactone,
local
treatments
hirsutism
In
addition
ascertaining
associated
comorbidities,
management
should
also
regular
follow-up
visits
planned
transition
care
providers.
Comprehensive
knowledge
regarding
pathogenesis
will
enable
earlier
identification
high
propensity
develop
PCOS.
Timely
implementation
individualized
improve
overall
adolescence,
prevent
quality
life.
Trends in Cardiovascular Medicine,
Год журнала:
2019,
Номер
30(7), С. 399 - 404
Опубликована: Сен. 4, 2019
Although
polycystic
ovary
syndrome
(PCOS)
is
one
of
the
most
common
endocrine
disorders
affecting
women,
its
etiology
not
entirely
understood.
Clinical
symptoms
PCOS
include
acne,
amenorrhea
or
oligomenorrhea,
hirsutism,
infertility,
and
mood
disorders,
which
tend
to
be
primary
focus
clinical
management.
However,
impact
on
future
cardiovascular
disease
(CVD)
risk
should
overlooked,
opportunities
implement
CVD
prevention
strategies
in
these
women
given
high
priority.
The
pathogenesis
commonly
involves
insulin
resistance
leads
several
cardiometabolic
abnormalities
(e.g.,
dyslipidemia,
hypertension,
glucose
intolerance,
diabetes,
metabolic
syndrome),
thereby
putting
at
an
increased
for
CVD.
Prior
studies
have
found
that
subclinical
markers
such
as
coronary
artery
calcium
scores,
C-reactive
protein,
carotid
intima-media
thickness,
endothelial
dysfunction
are
more
likely
with
PCOS.
While
associations
between
been
well
established,
whether
associated
CVD,
independently
factors,
clear.
Lifestyle
interventions
weight
management
may
mitigate
some
risks
encouraged.
This
review
summarizes
literature
factors
provides
recommendations
would
aid
clinicians
factors.
Abstract
More
than
1
out
of
10
women
worldwide
are
diagnosed
with
polycystic
ovary
syndrome
(PCOS),
the
leading
cause
female
reproductive
and
metabolic
dysfunction.
Despite
its
high
prevalence,
PCOS
accompanying
morbidities
likely
underdiagnosed,
averaging
>
2
years
3
physicians
before
diagnosed.
Although
it
has
been
intensively
researched,
underlying
cause(s)
have
yet
to
be
defined.
In
order
understand
pathophysiology,
developmental
origins,
how
predict
prevent
onset,
there
is
an
urgent
need
for
safe
effective
markers
treatments.
this
review,
we
detail
which
animal
models
more
suitable
contributing
our
understanding
etiology
pathophysiology
PCOS.
We
summarize
highlight
advantages
limitations
hormonal
or
genetic
manipulation
models,
as
well
naturally
occurring
PCOS-like
females.
PLoS Medicine,
Год журнала:
2020,
Номер
17(6), С. e1003132 - e1003132
Опубликована: Июнь 23, 2020
Background
Polycystic
ovary
syndrome
(PCOS)
is
a
common,
complex
genetic
disorder
affecting
up
to
15%
of
reproductive-age
women
worldwide,
depending
on
the
diagnostic
criteria
applied.
These
are
based
expert
opinion
and
have
been
subject
considerable
controversy.
The
phenotypic
variation
observed
in
PCOS
suggestive
an
underlying
heterogeneity,
but
recent
meta-analysis
European
ancestry
cases
found
that
architecture
defined
by
different
was
generally
similar,
suggesting
do
not
identify
biologically
distinct
disease
subtypes.
We
performed
this
study
test
hypothesis
there
relevant
subtypes
PCOS.
Methods
findings
Using
biochemical
genotype
data
from
previously
published
genome-wide
association
(GWAS),
we
investigated
whether
were
reproducible
with
subtype-specific
associations.
Unsupervised
hierarchical
cluster
analysis
quantitative
anthropometric,
reproductive,
metabolic
traits
genotyped
cohort
893
(median
interquartile
range
[IQR]:
age
=
28
[25–32],
body
mass
index
[BMI]
35.4
[28.2–41.5]).
clusters
replicated
independent,
ungenotyped
263
IQR:
[24–33],
BMI
35.7
[28.4–42.3]).
clustering
revealed
2
subtypes:
"reproductive"
group
(21%–23%),
characterized
higher
luteinizing
hormone
(LH)
sex
binding
globulin
(SHBG)
levels
relatively
low
insulin
levels,
"metabolic"
(37%–39%),
BMI,
glucose,
lower
SHBG
LH
levels.
GWAS
cohort,
limiting
either
reproductive
or
identified
alleles
4
loci
associated
subtype
at
significance
(PRDM2/KAZN,
P
2.2
×
10−10;
IQCA1,
2.8
10−9;
BMPR1B/UNC5C,
9.7
CDH10,
1.2
10−8)
one
locus
significantly
(KCNH7/FIGN,
1.0
10−8).
developed
predictive
model
classify
separate,
family-based
73
[25–33],
34.3
[27.8–42.3])
tended
families
carriers
reported
rare
variants
DENND1A,
gene
regulates
androgen
biosynthesis,
more
likely
Limitations
our
only
diagnosed
National
Institutes
Health
(NIH)
included,
sample
sizes
for
small,
replicated.
Conclusions
In
conclusion,
Furthermore,
these
novel,
knowledge,
susceptibility
loci.
Our
results
suggest
because
they
appear
architecture.
This
demonstrates
how
subtyping
can
be
used
gain
additional
insights
data.
Endocrine Reviews,
Год журнала:
2022,
Номер
43(6), С. 927 - 965
Опубликована: Янв. 13, 2022
Polycystic
ovary
syndrome
(PCOS)
is
among
the
most
common
disorders
in
women
of
reproductive
age,
affecting
up
to
15%
worldwide,
depending
on
diagnostic
criteria.
PCOS
characterized
by
a
constellation
interrelated
abnormalities,
including
disordered
gonadotropin
secretion,
increased
androgen
production,
chronic
anovulation,
and
polycystic
ovarian
morphology.
It
frequently
associated
with
insulin
resistance
obesity.
These
metabolic
derangements
cause
major
morbidities
across
lifespan,
anovulatory
infertility
type
2
diabetes
(T2D).
Despite
decades
investigative
effort,
etiology
remains
unknown.
Familial
clustering
cases
has
indicated
genetic
contribution
PCOS.
There
are
rare
Mendelian
forms
extreme
phenotypes,
but
typically
follows
non-Mendelian
pattern
inheritance
consistent
complex
architecture,
analogous
T2D
obesity,
that
reflects
interaction
susceptibility
genes
environmental
factors.
Genomic
studies
have
provided
important
insights
into
disease
pathways
current
criteria
do
not
capture
underlying
differences
biology
different
We
provide
state-of-the-science
review
analyses
PCOS,
an
overview
genomic
methodologies
aimed
at
general
audience
non-geneticists
clinicians.
Applications
will
be
discussed,
strengths
limitations
each
study.
The
contributions
factors,
developmental
origins,
reviewed.
Insights
pathogenesis
architecture
summarized.
Future
directions
for
outlined.
Journal of Clinical Medicine,
Год журнала:
2019,
Номер
8(10), С. 1606 - 1606
Опубликована: Окт. 3, 2019
Polycystic
Ovary
Syndrome
(PCOS)
is
a
complex
condition
with
mechanisms
likely
to
involve
the
interaction
between
genetics
and
lifestyle.
Familial
clustering
of
PCOS
symptoms
well
documented,
providing
evidence
for
genetic
contribution
condition.
This
overview
aims
firstly
systematically
summarise
current
literature
surrounding
PCOS,
secondly,
assess
methodological
quality
systematic
reviews
identify
limitations.
Four
databases
were
searched
candidate
gene
reviews,
was
assessed
AMSTAR
tool.
Genome-wide
association
studies
(GWAS)
identified
by
semi
structured
search.
Of
17
high
moderate
four
low
quality.
A
total
19
loci
have
been
associated
risk
in
GWAS,
11
these
replicated
across
two
different
ancestries.
Gene
located
neuroendocrine,
metabolic,
reproductive
pathways.
Overall,
most
robust
findings
THADA,
FSHR,
INS-VNTR,
DENND1A,
that
now
require
validation.
also
limitations
important
considerations
future
studies.
Much
work
remains
causal
variants
functional
relevance
genes
PCOS.
Reproductive Biology and Endocrinology,
Год журнала:
2022,
Номер
20(1)
Опубликована: Янв. 10, 2022
Abstract
As
a
common
endocrinopathy
of
reproductive-aged
women,
polycystic
ovary
syndrome
(PCOS)
is
characterized
by
hyperandrogenism,
oligo-anovulation
and
ovarian
morphology.
It
linked
with
insulin
resistance
through
preferential
abdominal
fat
accumulation
that
worsened
obesity.
Over
the
past
two
millennia,
menstrual
irregularity,
male-type
habitus
sub-infertility
have
been
described
in
women
confirm
these
clinical
features
PCOS
were
antiquity.
Recent
findings
normal-weight
hyperandrogenic
show
exaggerated
lipid
subcutaneous
(SC)
stem
cells
during
development
to
adipocytes
vitro
occurs
combination
reduced
sensitivity
highly-lipolytic
intra-abdominal
vivo.
This
phenotype
may
be
an
evolutionary
metabolic
adaptation
balance
energy
storage
glucose
availability
fatty
acid
oxidation
for
optimal
use
reproduction.
review
integrates
fundamental
endocrine-metabolic
changes
healthy,
similar
PCOS-like
traits
present
animal
models
which
tissue
differentiation
completed
fetal
life
as
humans
support
concept
has
ancestral
developmental
origins.
The Journal of Clinical Endocrinology & Metabolism,
Год журнала:
2019,
Номер
104(9), С. 3835 - 3850
Опубликована: Апрель 30, 2019
Polycystic
ovary
syndrome
(PCOS)
is
among
the
most
common
endocrine
disorders
of
premenopausal
women,
affecting
5%
to15%
this
population
depending
on
diagnostic
criteria
applied.
It
characterized
by
hyperandrogenism,
ovulatory
dysfunction,
and
polycystic
ovarian
morphology.
PCOS
highly
heritable,
but
only
a
small
proportion
heritability
can
be
accounted
for
genetic
susceptibility
variants
identified
to
date.