Rare Diseases Symptoms Automatic Extraction
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A random Abstract
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Disruption of autoregulatory feedback by a mutation in a remote, ultraconserved PAX6 enhancer causes aniridia.
[aniridia]
The
strictly
regulated
expression
of
most
pleiotropic
developmental
control
genes
is
critically
dependent
on
the
activity
of
long
-range
cis-regulatory
elements
.
This
was
revealed
by
the
identification
of
individuals
with
a
genetic
condition
lacking
coding-region
mutations
in
the
gene
commonly
associated
with
the
disease
but
having
a
variety
of
nearby
chromosomal
abnormalities
,
collectively
described
as
cis-ruption
disease
cases
.
The
congenital
eye
malformation
aniridia
is
caused
by
haploinsufficiency
of
the
developmental
regulator
PAX
6
.
We
discovered
a
de
novo
point
mutation
in
an
ultraconserved
cis-element
located
150
kb
downstream
from
PAX
6
in
an
affected
individual
with
intact
coding
region
and
chromosomal
locus
.
The
element
SIMO
acts
as
a
strong
enhancer
in
developing
ocular
structures
.
The
mutation
disrupts
an
autoregulatory
PAX
6
binding
site
,
causing
loss
of
enhancer
activity
,
resulting
in
defective
maintenance
of
PAX
6
expression
.
These
findings
reveal
a
distinct
regulatory
mechanism
for
genetic
disease
by
disruption
of
an
autoregulatory
feedback
loop
critical
for
maintenance
of
gene
expression
through
development
.
