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
"b cells"
symptom
omenn syndrome
severe combined immunodeficiency
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom