Background Thediseasefirstappearedinthemedical - - PowerPoint PPT Presentation

Background







The
disease
first
appeared
in
the
medical
 literature
when
endocrinologists
Prader,
 Labhart,
and
Willi
published
a
report
 describing
an
unusual
pattern
of
 abnormalities.

Because
of
this
report,
the
 disease
got
its
name,
Prader‐Willi
Syndrome.


Introduction


What
is
Prader‐Willi
Syndrome?


• PWS
is
characterized
by
diminished
fetal
activity,

• besity,
muscular
hypotonia,
mental
retardation,


short
stature,
hypogonadotropic
hypogonadism,
 and
small
hands
and
feet.


Symptom


• Behavioral
problems,
usually
during


transitions
and
unanticipated
changes,
such
 as
stubbornness
or
temper
tantrums



• Delayed
motor
skills
and
speech

• Cognitive
problems,
ranging
from
near


normal
intelligence
to
mild
mental
 retardation;
learning
disabilities
are
common



• Low
sex
hormone
levels


The
Genetic
Changes
Related
to
PWS


Most
cases
of
PWS
 (about
70
percent)


• ccur
when
the


segment
11‐13
of
the
 paternal
 chromosome
15
is
 deleted
in
each
cell.

The
region
is
called
Prader‐Willi
syndrome
 chromosome
region
(PWCR).
It
includes
 the
following
genes:


• SNRPN
gene









SNRPN
gene
is
also
known
as
SM‐D.
The
protein


encoded
by
this
gene
is
one
polypeptide
of
a
small
 nuclear
ribonucleoprotein
complex.









The
protein
plays
a
role
in
 pre‐mRNA
processing,
 possibly
tissue‐specific
 alternative
splicing
events.
 The
5'
UTR
of
this
gene
has
 been
identified
as
an
 imprinting
center.
Alternative
 splicing
or
deletion
caused
by
 a
translocation
event
in
this
 paternally‐expressed
region
is
 responsible
for
Prader‐Willi
 switch
failure. syndrome
due
to
parental
imprint

Necdin
gene







This
intronless
gene
is
 located
in
the
Prader‐Willi
 syndrome
deletion
 region.
It
is
an
imprinted
 gene
and
is
expressed
 exclusively
from
the
 paternal
allele.
The
 protein
coded
by
the
 gene
maintains
the
dTMP
 pool
critical
for
DNA replication
and
repair.
Studies
in
mouse
suggest
that
the
 protein
may
suppress
growth
in
postmitotic
neurons.

Continue


• In
another
25
percent
of
cases,
a
person
with


PWS
has
two
copies
of
chromosome
15
inherited
 from
his
or
her
mother
instead
of
one
copy
from
 each
parent.
This
phenomenon
is
called
maternal
 uniparental
disomy.


• Rarely,
PWS
can
also
be
caused
by
a


chromosomal
rearrangement
called
a
 translocation,
or
by
a
mutation
or
other
defect
 that
abnormally
turns
off
genes
on
the
paternal
 chromosome
15.


Stages
of
Development


Infancy
 Babies
with
PWS
are
very
floppy
at
birth,
and
 the
ability
to
suck
is
weak
or
absent.

 Childhood
 




Some
time
between
the
ages
of
one
and
four
 years,
children
with
PWS
begin
to
show
a
 heightened
interest
in
food
and
in
severe
 cases
develop
what
appears
to
be
an
 insatiable
appetite,
so
that
they
will
try
to


• btain
food
by
any
means
possible.


Adolescence
 





People
with
PWS
do
not
usually
reach
full
 sexual
development,
and
there
have
been
only
 three
cases
worldwide
of
a
woman
with
PWS
 having
a
child.
However
there
may
be
cases
of
 which
doctors
are
unaware.
 Life
as
an
adult
 





As
adults,
people
with
PWS
have
varying
 abilities
in
attaining
independence,
although
all
 will
need
some
form
of
support
or
monitoring
 to
help
with
controlling
their
food
intake,
and
 thus
their
weight.


The
probability
of
inheritance
of
PWS


• Most
cases
of
PWS
are
not
inherited,
particularly


those
caused
by
a
deletion
in
the
paternal
 chromosome
15
or
by
maternal
uniparental
disomy.
 These
genetic
changes
occur
as
random
events
 during
the
formation
of
reproductive
cells
(eggs
and
 sperm)
or
in
early
embryonic
development.
Affected
 people
typically
have
no
history
of
the
disorder
in
 their
family.


• Rarely,
a
genetic
change
responsible
for
PWS
can
be


inherited.
For
example,
it
is
possible
for
a
genetic
 defect
that
abnormally
inactivates
genes
on
the
 paternal
chromosome
15
to
be
passed
from
one
 generation
to
the
next.


Diagnosis


• A
suspected
diagnosis
of
PWS
is
usually
made
by
a


physician
based
on
clinical
symptoms.
The
 diagnosis
is
then
confirmed
by
a
blood
test.
Two
 types
of
tests
can
be
used
to
confirm
the
 diagnosis.


• A
"FISH"
(fluorescent
in
situ
hybridization)
test
will


identify
those
patients
with
PWS
due
to
a
deletion,
 but
will
not
identify
those
who
have
PWS
by
 "UPD"
(uniparental
disomy)
or
via
an
imprinting
 error.


Continue


• Methylation
analysis
will
detect
all
three
forms

• f
PW,
so
if
PWS
is
suspected
but
a
FISH
test
is


negative,
a
DNA
methylation
test
is
warranted.



• Almost
all
cases
of
PWS
can
be
confirmed
by
one

• f
the
above
tests.
However,
in
the
rare
event


that
laboratory
tests
do
not
confirm
PWS,
a
 clinical
diagnosis
can
be
helpful
for
the
 development
of
a
management
plan.



Treatment


• PWS
cannot
be
cured.
But,
early
intervention
can
help


people
build
skills
for
adapting
to
the
disorder.

Early
 diagnosis
can
also
help
parents
learn
about
the
 condition
and
prepare
for
future
challenges.
A
health
 care
provider
can
do
a
blood
test
to
check
for
PWS.



• Exercise
and
physical
activity
can
help
control
weight


and
help
with
motor
skills.

Speech
therapy
may
be
 needed
to
help
with
oral
skills.



• Human
growth
hormone
has
been
found
to
be
helpful


in
treating
PWS.

It
can
help
to
increase
height,
 decrease
body
fat,
and
increase
muscle
mass.

 However,
no
medications
have
yet
been
found
to
 control
appetite
in
those
with
PWS.



In
the
Future


• To
do
more
researches
about
Prader‐Willi


Syndrome
and
find
out
others
genes
related
 to
it.


• To
do
a
natural
experiment
of
PWS
in
order
to


better
understand
the
disease.


References


• The
website
of
the
Prader‐Willi
Syndrome
Association(UK)


http://pwsa.co.uk/main.php?catagory=1
 







http://www.pwsa.co.uk/main.php?catagory=1&sub_catagory=1


• National
Center
for
Biotechnology
Information


http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section. 182&ref=toc


• http://www.ncbi.nlm.nih.gov/gene/4692?
• rdinalpos=1&itool=EntrezSystem2.PEntrez.Gene.Gene_Results

Panel.Gene_RVDocSum


• http://www.ncbi.nlm.nih.gov/books/bv.fcgi?

call=bv.View..ShowSection&rid=gnd.section.287


• http://www.ncbi.nlm.nih.gov/sites/entrez?

a=gene&Cmd=ShowDetailView&TermToSearch=7298


• http://www.ncbi.nlm.nih.gov/gene/6638?
• rdinalpos=1&itool=EntrezSystem2.PEntrez.Gene.Gene_Results

Panel.Gene_RVDocSum


Acknowledgements


• Ms.
McMahon

• Prof.
Brennan

• Dr.
Sat

• Harlem
Children
Society

• National
Library
of
Medicine

• Bronx
Community
College