Rare Diseases Symptoms Automatic Extraction
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A random Abstract
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Human syndromes of immunodeficiency and dysregulation are characterized by distinct defects in T-cell receptor repertoire development.
[omenn syndrome]
Human
immunodeficiencies
characterized
by
hypomorphic
mutations
in
critical
developmental
and
signaling
pathway
genes
allow
for
the
dissection
of
the
role
of
these
genes
in
the
development
of
the
T
-
cell
receptor
(
TCR
)
repertoire
and
the
correlation
of
alterations
of
the
TCR
repertoire
with
diverse
clinical
phenotypes
.
The
presence
of
T
cells
in
patients
with
Omenn
syndrome
(
OS
)
and
patients
with
atypical
presentations
of
severe
combined
immunodeficiency
gene
mutations
presents
an
opportunity
to
study
the
effects
of
the
causal
genes
on
TCR
repertoires
and
provides
a
window
into
the
clinical
heterogeneity
observed
.
We
performed
deep
sequencing
of
TCRβ
complementarity-determining
region
3
(
CDR
3
)
regions
in
subjects
with
a
series
of
immune
dysregulatory
conditions
caused
by
mutations
in
recombination
activating
gene
1
/
2
(
RAG
1
/
2
)
,
IL
-
2
receptor
γ
(
IL
2
RG
)
,
and
ζ
chain-associated
protein
kinase
70
(
ZAP
70
)
;
a
patient
with
atypical
DiGeorge
syndrome
;
and
healthy
control
subjects
.
We
found
that
patients
with
OS
had
marked
reductions
in
TCRβ
diversity
compared
with
control
subjects
,
as
expected
.
Patients
with
atypical
presentations
of
RAG
or
IL
2
RG
mutations
associated
with
autoimmunity
and
granulomatous
disease
did
not
have
altered
overall
diversity
but
instead
had
skewed
V-J
pairing
and
skewed
CDR
3
amino
acid
use
.
Although
germline
TCRs
were
more
abundant
and
clonally
expanded
in
patients
with
OS
,
nongermline
sequences
were
expanded
as
well
.
TCR
β
from
patients
with
RAG
mutations
had
less
junctional
diversity
and
smaller
CDR
3
s
than
patients
with
OS
caused
by
other
gene
mutations
and
healthy
control
subjects
but
relatively
similar
CDR
3
amino
acid
use
.
High
-throughput
TCR
sequencing
of
rare
immune
disorders
has
demonstrated
that
quantitative
TCR
diversity
can
appear
normal
despite
qualitative
changes
in
repertoire
and
strongly
suggests
that
in
human
subjects
RAG
enzymatic
function
might
be
necessary
for
normal
CDR
3
junctional
diversity
.