Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Analysis of mutations from SCID and Omenn syndrome patients reveals the central role of the Rag2 PHD domain in regulating V(D)J recombination.
[omenn syndrome]
Rag
2
plays
an
essential
role
in
the
generation
of
antigen
receptors
.
Mutations
that
impair
Rag
2
function
can
lead
to
severe
combined
immunodeficiency
(
SCID
)
,
a
condition
characterized
by
complete
absence
of
T
and
B
cells
,
or
Omenn
syndrome
(
OS
)
,
a
form
of
SCID
characterized
by
the
virtual
absence
of
B
cells
and
the
presence
of
oligoclonal
autoreactive
T
cells
.
Here
,
we
present
a
comparative
study
of
a
panel
of
mutations
that
were
identified
in
the
noncanonical
plant
homeodomain
(
PHD
)
of
Rag
2
in
patients
with
SCID
or
OS
.
We
show
that
PHD
mutant
mouse
Rag
2
proteins
that
correspond
to
those
found
in
these
patients
greatly
impaired
endogenous
recombination
of
Ig
gene
segments
in
a
Rag
2
-
deficient
pro-
B
cell
line
and
that
this
correlated
with
decreased
protein
stability
,
impaired
nuclear
localization
,
and
/
or
loss
of
the
interaction
between
Rag
2
and
core
histones
.
Our
results
demonstrate
that
point
mutations
in
the
PHD
of
Rag
2
compromise
the
functionality
of
the
entire
protein
,
thus
explaining
why
the
phenotype
of
cells
expressing
PHD
point
mutants
differs
from
those
expressing
core
Rag
2
protein
that
lacks
the
entire
C-
terminal
region
and
is
therefore
devoid
of
the
regulation
imposed
by
the
PHD
.
Together
,
our
findings
reveal
the
various
deleterious
effects
of
PHD
Rag
2
mutations
and
demonstrate
the
crucial
role
of
this
domain
in
regulating
antigen
receptor
gene
assembly
.
We
believe
these
results
reveal
new
mechanisms
of
immunodeficiency
in
SCID
and
OS
.
Diseases
Validation
Diseases presenting
"immunodeficiency"
symptom
adrenal incidentaloma
allergic bronchopulmonary aspergillosis
cushing syndrome
dracunculiasis
hirschsprung disease
hodgkin lymphoma, classical
homocystinuria without methylmalonic aciduria
kabuki syndrome
legionellosis
malignant atrophic papulosis
oculocutaneous albinism
omenn syndrome
papillon-lefèvre syndrome
primary effusion lymphoma
primary hyperoxaluria type 1
pyomyositis
severe combined immunodeficiency
sneddon syndrome
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated