Evaluation of phenotypic abnormalities among patients with intellectual disability
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Issue Date
2016-09-01
Language
en
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Abstract
The
development
of
more
advanced
genetic
techniques
like
the
SNP-‐array
and
genome
wide
sequencing
techniques
contributed
largely
to
the
identifying
of
genetic
causes
of
intellectual
disability.
Interpretation
of
the
genetic
variations
found
with
these
techniques,
however,
remains
difficult.
Multiple
patients
with
the
same
phenotype
and
genotype
are
needed
to
decide
about
a
variant’s
pathogenicity.
It
is
although
difficult
to
determine
how
many
patients
are
needed
for
a
statistic
significant
conclusion.
More
information
about
the
specificity
of
phenotypic
features
will
greatly
improve
these
considerations,
as
genetic
variants
in
combination
with
rare
features
can
be
declared
pathogenic
when
fewer
patients
are
found
than
variants
occurring
in
combination
with
common
features.
However,
at
the
moment
no
comprehensive
overview
of
the
phenotype
of
patients
with
ID
is
available.
This
article
provides
an
overview
of
the
specificity
of
phenotypic
features
by
an
extensive
evaluation
of
the
phenotype
of
a
large
cohort
of
7407
well-‐defined
patients
with
ID.
From
1320
of
these
patients
very
detailed
information
was
available,
these
patients
formed
a
best-‐
defined
group
used
for
the
analyses,
the
other
6087
a
well-‐defined
replication
cohort
An
overview
of
the
frequency
of
all
Human
Phenotype
Ontology
(HPO)
features
in
these
patients
is
presented.
In
addition
we
found
1534
combinations
of
positively
associated
features.
These
associations
consisted
of
expected
associations
like
Cleft
lip
(HP:0000204)
and
Cleft
palate
(HP:0000175)
(P<0,001)
but
also
unexpected
associations
like
Short
stature
(HP:0004322)
and
Abnormality
of
the
forebrain
HP:0100547)
(P<0,001).
Most
of
these
1534
combinations
were
also
associated
in
the
replication-‐cohort.
We
also
proofed
that
half
of
the
major
anomalies
registered
by
Eurocat
occur
more
in
patients
with
intellectual
disability
than
in
the
normal
population
and
that
patients
with
more
congenital
anomalies
have
a
higher
chance
of
having
facial
dysmorphism.
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