Transcript Power Point Presentationx

Professor Brennan
Ms. McMahon
Bronx Community College
PRADER-WILLI SYNDROME
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,
obesity, 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)
occur 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 syndrome due to parental imprint
switch failure.
Necdin gene
This intronless gene is
located in the PraderWilli 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.
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 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
obtain 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.
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 Methylation analysis will detect all three forms
of 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
of 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)
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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?ordinalpos=1&itool=Ent
rezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowS
ection&rid=gnd.section.287
http://www.ncbi.nlm.nih.gov/sites/entrez?a=gene&Cmd=ShowD
etailView&TermToSearch=7298
http://www.ncbi.nlm.nih.gov/gene/6638?ordinalpos=1&itool=Ent
rezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Acknowledgements
 Ms. McMahon
 Prof. Brennan
 Dr. Sat
 Harlem Children Society
 National Library of Medicine
 Bronx Community College