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Research

RESEARCH OPPORTUNITY!    CHOP is doing a prenatal PKS study.  Please click below to access papers to complete if you'd like to participate (7-2016)

PKS Prenatal Survey

Medical Release Form

Having your child's prenatal records and all growth charts will be very helpful. Please print, complete and mail to:

Sarah Noon

3615 Civic Center Blvd

Abramson Research Center, Rm 1007B

Philadelphia, PA 19104

 

PKS Kids is proud to collaborate with several specialists in on-going research, both through donations and data. Research information and published papers are linked below, newest to oldest.


Kaur et al PKS arrays PLoSOne 2014

A description of the above paper from Dr. Ian Krantz.

This paper looks at the effect of having the extra copies of chromosome 12p on the whole cell and by extension on the whole individual.  Like many diagnoses where there are many systems involved (e.g. Heart defects, hearing loss, seizures, cleft palates, diaphragmatic hernias, limb differences, growth differences, intellectual and learning differences, etc…) - we believe that the primary underlying difference (in PKS it would be having the extra copies of chromosome 12p) act as a “master switch” and effects a lot of downstream things in any given cell in which it exists.   Since the main “director” of how our cells grow and differentiate are genes one of the important things to understand in any given diagnosis is what is the effect of the main change (again in PKS having extra copies of 12p) is on all of the other genes (of which there are around 20,000) in these cells.  So, to take a step back: we all start out as a single cell (after the egg and the sperm come together) - as that first cell starts to divide, somehow these daughter cells are signaled to differentiate into different cell types (e.g. Heart cells, brain cells, muscle cells, etc…).  So how does this happen?  It is complicated but to simplify: all of our cells have the exact same DNA and therefore the exact same genes – so how does a heart cell suddenly arise from an undifferentiated cell and how does a nerve cell arise? - This happens by the cells turning on or off (at different levels) the genes (the level at which a gene's product is turned on or off is called its “expression level” - genes are the blueprints for all of the proteins in our cells (proteins are the actual structural components of our cells) - to make a protein from a gene there is an intermediate product called a transcript made up of RNA, which is the template that proteins are made on and the level (or expression) of these transcripts is what regulates what a cell will become).  The very precise and careful regulation of gene expression is needed for cells to grow and differentiate into different cell types, tissues and organs.  With new technology we are able to take cells from an individual and look at the pattern of expression of all genes in the genome (all 20,000 genes) and see how their expression levels compare to unaffected individuals (“normal” controls).  This tells us which genes are turned on too high or too low and gives us insight into which genes are dysregulated and may be the actual causes of the constellation of differences seen in a diagnosis such as PKS.  While the master switch difference is still the extra copies of 12p – we believe that there are genes on 12p that when present in extra copies cause many downstream genes throughout the genome to be dysregulated (some gene products play key roles in regulating (turning up or down) other genes – in developmental diagnoses like PKS, often key genes that act in this way are the master switches that are not acting properly.

So in this paper we looked at a bunch of samples from children with PKS and measured how much all of the genes in the genome were turned up or down too much or too little and found a list of a few hundred genes that are critically dysregulated – we then ask if any of these dysregulated genes could explain the individual features seen in constellation in PKS (e.g. Is there a critical gene that might explain the growth issues, is there another key dysregulated gene that might explain the heart defects, etc…).

 

So this work is important (we feel) for a number of reasons:

  1. On a purely scientific level it provides insight into what is important for normal human growth and development and what genes are critical for that – this would be of interest to many scientists for a number of obvious reasons including understanding how cells grow and differentiate, understanding important factors in the development of different cell types and tissues, and understanding basis issues of regulation of gene expression.
  2. From a PKS perspective it allows insight into what is going on a very basic molecular level and what is happening in these kids that is resulting in the differences we are seeing – the hope of all of this will be that if we find the individual causes of the constellation of difference seen in kids with PKS we can eventually develop very targeted therapies for some of the features – those clinical features that will lend themselves to treatment approaches postnatally would be the more physiological and ongoing developmental issues such as growth, muscle tone, seizures and even potential to develop therapies that would improve cognition and behavior…
  3. If we identify downstream genes that are critical for certain aspects of PKS (e.g. Heart defects) - then that gene may be very important for heart development and when altered may result in isolated heart defects in other individuals – since isolated heart defects are very common – this work may have a broader impact for populations with isolated birth differences that are seen in constellation in kids with PKS (e.g. For kids with isolated cleft palates, or isolated heart defects, or isolated intellectual disability/autism etc….)
  4. An indirect benefit is also just understanding how studying a rare diagnosis like PKS can lend insight into human development and hopefully this will interest and exciyt either investigators to study PKS and further this work along faster with higher profile to both bring awareness to PKS as well as to expedite and breakthroughs diagnostically or therapeutically .

Cardiology paper February 2014

We are thrilled to announce six new papers being published by the doctors at Children's Hospital of Philadelphia.  Here is a note from Dr. Ian Krantz and the documents. Thank you to all the doctors at CHOP for believing in our cause and our children!

Dear All, I am happy to report that all of the PKS articles are finally in press!  They are available on line currently and will come out in next months (December's) issue of the American Journal of Medical Genetics A.  I have attached pdfs of all of the articles .My deepest thanks to the Foundation and all of the families who have supported this work over the years and a special thanks to Dr. Pallister for his efforts to make this happen and to Dr. Kosuke Izumi who really helped finalize all of these articles and push all of us to get them published !A little Thanksgiving gift! Have a great Holiday all, Ian


Candee et al PKS and Seizures AJMG 12-12

Izumi et al Dup 12p and PKS AJMG 12-12

Conlin et al SNP arrays and PKS AJMG 12-12

Kostanecka et al Development in PKS AJMG 12-12

Pallister PKS Overview AJMG 12-12

Wilkens et al PKS Clinical Overview AJMG 12-12


List of published articles and journals regarding Pallister-Killian Syndrome

(Thanks to Nic Acquarola for compiling)


Seizure Study being done by Utah Pediatric Neurologist
PKS Kids is fortunate to be working with Dr. Francis Filloux in regard to seizure activity in our children. Attached is a survey that Dr. Filloux would like interested parents to complete and email or mail back to him. If you complete it in Word you may save and attach to an email.

Dr Filloux's contact information is:
Francis M. Filloux, MD
Division Chief, Pediatric Neurology
University of Utah School of Medicine

Francis.Filloux@hsc.utah.edu
801-587-7466

Parental Authorization

Take the survey! 
Word Version

Please let us know if you have any questions!


Grant/Research Letter

Letter from Dr. Krantz
Soon we hope to be able to post the published research from doctors at Children's Hospital of Philadelphia (CHoP). In the meantime, here is a letter from Dr. Krantz describing their goals and how you can assist the research.
Sarah P study
Here is an exciting new study done by doctors in Australia.
In May 2010 PKS Kids made a donation to CHoP to assist with research of Pallister-Killian Syndrome.
Dear Mrs. Hettiger,
This is tremendous! Thanks so much for your generosity and emphasizing PKS Kids' commitment to research! These funds will be put to direct use in our project to identify the exact genes that are dysregulated (turned up or down) in kids with PKS as a result of the extra chromosome 12 material as well as to help establish a comprehensive clinical database. This will lay the groundwork towards identifying targets for what we hope will be eventual therapeutic options for kids with PKS. Your organization and your kids have been an inspiration to us in our work and we hope that our work will result in a better understanding and clinical outcome for individuals and families affected by PKS.
With deepest heartfelt gratitude from our team here at CHOP!
Sincerely,
Ian
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