Issue #14
November 2011
In This Issue
Check Your Mailbox
DBAR Update
DBA Support Group
Show Us Your Logo!
DBA Fact
Happy Thanksgiving
DBAF Journal Club
Coming Soon...
Check Your Mailbox!
The Diamond Blackfan Anemia Foundation (DBAF) is
committed to keeping you updated and connected to the
entire DBA community. The Diamond Blackfan Anemia
Foundation is YOUR Foundation! We encourage you to
share your ideas, photos, and stories for our website and
upcoming newsletters. Contact us at
DBAFoundation@juno.com.
The Diamond Blackfan Anemia
Registry Update
by Eva Atsidaftos, MA, CCRP
DBAR Research Coordinator
Greetings from the Diamond Blackfan Anemia Registry (DBAR)!
For those
who are not familiar with who we are, the
DBAR is a research organization dedicated
to studying Diamond Blackfan anemia in
order to improve our understanding of this
very rare disorder, to educate families and
physicians, and to ultimately improve
treatment options. We accomplish this by
The Diamond Blackfan Anemia Foundation is
collecting and analyzing medical
committed to supporting DBA patients, families,
and research. It is only through the support of our information on DBA patients. This research
could not have been possible if it weren't for
friends and families that we can continue to fulfill
all the patients that are registered in the
our mission. We need your help!
DBAR, so thank you to all those that have
Eva Atsidaftos
enrolled.
As DBA families, each one of us shares the
challenges of living with a rare disorder, as well as
the hope for better treatment options and
ultimately, a cure. By working together, the DBAF
hopes to continue funding critical research,
supporting scientific conferences, sponsoring Camp
Sunshine, and providing our families with
information.
This has been a very exciting year for the DBAR. We have seen
much progress in improving our understanding of this very rare
disorder, DBA.
Some highlights of the DBAR Research Accomplishments for
Your partnership with us is essential to the DBAF's
success and growth. Your support allows us to
fund independently reviewed and approved
research projects from around the world and
provide information and support to our patients
and families. We rely on you for your important
financial support and your involvement.
In the next few weeks, you will be receiving
information on how YOU can make a difference.
Watch your mail box for this important
information. We are hopping for YOUR
participation.
The Diamond Blackfan Anemia Foundation
sincerely thanks our families and friends for their
generosity, hard work and continued efforts. It is
because of their commitment that we are able to
fulfill our mission for patients... for families... for
research.
2010-2011

Enrolled 14 new subjects in the DBAR (a 2.3% increase
from last year)

Updated the demographic, treatment response, and
clinical information for 621 existing patientsenrolled in
the DBAR

Continued to serve as a resource for information to
patients, families, physicians, collaborators, and health
care professionals

Continued the collection and storage of DNA and cell
lines from DBA patients and their families in the DBA
Biorepository; currently we have acquired 156 blood
samples from DBA affected patients and 240 family
members. These samples serve as a resource for
collaborative studies that will help identify the gene
abnormalities that cause DBA.

Analyzed the risk of cancer for DBA patients in
collaboration with the National Cancer Institute:
o Cancer and myelodysplasia were identified in
22 patients with DBA. One patient had 2
malignancies and myelodysplasia for a total of
24 events.
o Results were presented at the annual meeting
of the American Society of Pediatric
Hematology/Oncology in April 2011.
o The manuscript has been submitted for
publication.

Facilitated the discovery of one more DBA gene
(RPL26) and six potential candidate genes of unknown
significance, that also encode for ribosomal proteins, in
collaboration with Children's Hospital Boston. The
DBAR assisted by procuring samples for the Gene
Discovery project. An oral presentation was made at the
annual meeting of the American Society of Hematology
in December 2010. Again the manuscript has been
submitted for publication.

Continued gene discovery efforts for patients are
ongoing to aid in diagnosis and potentially assist in
treatment options in the future
o In 2008 a DNA Resequencing & Genotyping
Program grant was awarded to the DBAR
through the National Heart, Lung, and Blood
Institute to resequence all 80 ribosomal protein
genes; the results were analyzed in 2010.
o In collaboration with the National Human
Genome Research Institute and Johns Hopkins
University, we analyzed a group of patients
who did not have any mutations found from
the resequencing project. This time a different
method was used that looks for deletions
To ensure that you are receiving all the
current information, please be certain that
your contact information is up to date. Visit
our secure website and register today!
http://www.dbafoundation.org/registration.php
THANK YOU!
Upcoming Events
DBA Support Group
November 30, 2011
7:00 - 8:30pm
New Hyde Park, NY
Contact:
Ellen Muir
emuir@nshs.edu
1.877.DBA.NURSe
Ongoing Fundraisers
o
Mixed Bags Designs
Contact:
Vickie Lamb
Use Code: 69293
To order online visit:
o
http://www.mixedbagdesigns.com/
o
Wristbands Available
Contact:
Twila Edwards

Invited to write "How I Treat DBA" for the journal
Blood; published in November 2010 and distributed to
physicians, other health care professionals and families
as a source document

Embarked on three clinical treatment research protocols
for transfusion-dependent DBA patients; two of which
will open by December 2011
o The amino acid Leucine is to be offered to
transfusion- dependent patients over age 2 years
o A new "bone-building" drug which was found to
have a side effect of increasing the patients' hemoglobin
(a desirable effect for DBA patients) will be open to
adult transfusion-dependent DBA patients to see if
indeed it will decrease their transfusion requirement.

Numerous manuscripts and abstracts have been
published during the past funding period through
collaborative studies with the DBA Registry:
twilak@cox.net
Tribute Cards Available
(2 styles)
(missing genes).
Multiple DBA patients were found to have
deletions of previously known DBA genes,
thus confirming their diagnosis. A poster
presentation was made at the annual meeting of
the American Society of Hematology in
December 2010 and the manuscript will be
published in the journal Blood in Dec 2011.
From the resequencing project, one transfusion
dependent patient was found to not have DBA,
but instead have another disorder, 5qmyelodysplastic syndrome (MDS). The patient
was placed on lenalidomide; a drug that is
known to be effective in 5q-MDS, and the
patient went into remission (not requiring any
transfusions). This finding was reported as an
oral "late-breaking" presentation at the annual
meeting of the American Society of
Hematology in December 2010.
A protocol to perform whole exome
sequencing (WES) (which looks at all the
genes and for associations to DBA) on patients
without identified mutations or deletions has
been written in collaboration with the National
Human Genome Research Institute, and has
received funding from the Diamond Blackfan
Anemia Foundation; final institutional review
board approval pending.
The DBAR would like to take this opportunity to thank the DBA
Foundation and DBA Canada, for awarding us with funding to
further support our endeavors. We would also like to thank all the
families who have worked so hard to make all this funding
possible.
In honor of...
In memory of...
We would also like to take this opportunity to invite all patients to
Contact:
join us in these research efforts. Being that DBA is such a rare
condition, it is imperative that every DBA patient enroll in the
DBAR.
Dawn Baumgardner
dbaumgardner@dbafoundation.org
716.674.2818
Please feel free to call or email me to request Registry enrollment
forms or to check on the status of your enrollment.
Contact:
Eva Atsidaftos/ DBAR Research Coordinator
Email: eatsidaf@nshs.edu
Toll free: 888-884-DBAR (3227)
DBA Support Group - New York
DBA Cookbooks Available
Contact:
Betty Lightner
betty.lightner@gmail.com
To download your order form:
http://issuu.com/bhivemom/docs/cookbook_order
_form-pdf
Good Search/Good Shop
Raise money for DBAF just by searching the web
and shopping online!
Just download the GoodSearch - Diamond Blackfan
Anemia Foundation - DBAF toolbar at
http://www.goodsearch.com/toolbar/diamondblackfan-anemia-foundation-dbaf
Quick Links
Make a Donation
Our Website
Join the DBA Yahoo Group
:: 716-674-2818
Take the Challenge ~ Show Us
Your Logo
T-shirts, hats,
coffee mugs, face
paintings, tattoos,
bags, pumpkins ...
our logo is showing
up everywhere! We
are thrilled that our
beautiful logo is
proudly being worn
and displayed by
patients, families,
and friends.
Kevin Gately's life and legacy live on in the hearts of those
who knew and loved him and in the hearts of his DBA
family. Kevin's family continues to honor his memory
through their dedication to the Kevin J Gately Foundation.
Kevin's tragic death on July 26, 2010, just five days after
his 29th birthday, from complications of iron overload
motivated their efforts to keep Kevin's memory alive. This
year's golf outing held on October 17 was yet another
testament to the commitment the Thompson and Gately
families have to Diamond Blackfan Anemia and our
families. The event raised $6,500 for the DBAF and a
$2,000 family sponsorship for a DBA family to attend Camp
Sunshine. We are humbled and honored to accept this
heartfelt donation.
Here's the challenge: we'd like to see how many
places we can show off our
logo! Snap a picture sporting
our logo and send us your story.
Draw it, print it out, wear it,
wave it, tattoo it, carve it... be
creative! Take us to school, on
vacation, to the hospital, on a
plane, to the game, in your
home... anywhere! Show us
your logo! Send your photos
and stories to DBAFoundation@juno.com.
DBA Fact #7
Our Facebook page posts DBA facts written
by DBA nurse, Ellen Muir, RN, MSN, CPON.
We are pleased to share these fast facts with
our patients and families. Thanks, Ellen!
The Bone Marrow Examination- What is it
and Why should it be done?
Ellen Muir
The bone marrow is the "factory" where
hematopoiesis takes place (that is a fancy word for the production
of the cells in the blood - red blood cells, white blood cells and
platelets). A bone marrow examination is a test that looks at the
cells in the bone marrow, to see how many there are and what they
look like. The bone marrow is found in the center of the bones and
is made up of both spongy bone and liquid marrow.
Most of the time, the information from the bone marrow exam can
be useful in diagnosing DBA and rule out other disorders which
may cause a change in the marrow (such as leukemia, aplastic
anemia or myelodysplastic syndrome [MDS]). A bone marrow
examination is usually done to make the initial diagnosis of DBA.
If this hasn't been done, it is recommended to be done before
starting steroids as the medicine can change the appearance of the
cells. Aplastic anemia, acute leukemia and MDS have been
reported in DBA. For this reason, we perform a bone marrow
evaluation if there is a change in blood counts seen on the
complete blood counts (CBC), such as a steady decrease in white
blood cell count or platelet count. We do not perform routine
yearly bone marrow exams in patients whose blood counts are
stable and have not changed.
A Bone Marrow Aspirate is usually done from the posterior (back)
hip (iliac) bone. Rarely it can be done from the anterior (front) hip
bone or the chest bone (sternum). The area to be used is numbed
with a topical anesthetic, usually lidocaine. The area is then
sterilely cleaned and a needle is placed into the bone. Liquid
marrow is removed with a syringe and sent for the following tests:
Morphology of the bone marrow is usually done by the
hematologist or the pathologist or both. This is where the bone
marrow is spread on a slide and stained with special stains that will
"color" the blood cells, making them easier to identify under the
microscope. The cells are counted and viewed for their appearance.
Abnormalities in the number of cells can give information about
potential Aplastic anemia (too few cells of all three cell lines) and
abnormalities in their shapes or sizes can be important to diagnose
myelodysplastic syndrome or leukemia. Cytogenetics is the study
of the structure of DNA within the cell nucleus. This is done in two
parts:
Karyotype gives information about the number of chromosomes. A
normal person has 23 pairs of chromosomes; one of those pairs is
XX (female) or XY (male). An extra chromosome (trisomy) or a
missing chromosome (monosomy) will indicate a disease process
(for example, an extra chromosome 21 is associated with Down
Syndrome). Fluorescence in situ hybridization (FISH) provides
researchers with a way to see and map the genetic material in an
individual's cells, including specific chromosomes or portions of
chromosomes.
A Bone Marrow Biopsy can be done at the same time as the bone
marrow aspirate. A piece of the spongy bone is removed, usually
using the same needle and puncture area. The biopsy specimen is
removed and sent to pathology for:
Cellularity - This is the percentage of cells in the specimen. Bone
marrow contains hematopoietic stem cells and fat cells. If a sample
is hypocellular, it has fewer than the expected number of
hematopoietic cells (cells that mature into red blood cells, white
blood cells and platelets). If a sample is hypercellular, it has more
than the expected number of hematopoietic cells. Cellularity is age
dependent -in newborns, all marrow is hematopoietic (shows 100%
cellularity). With age, hematopoiesis (the number of cells)
decreases, and the amount of fat increases. Normal cellularity of an
adult bone marrow ranges between 30-70% and changes under
pathological conditions- a marrow is reported as hypercellular
(over 70%), normocellular (30-70%) or hypocellular (under 30%).
If you have any questions, please don't hesitate to contact me or
speak to your doctor.
Ellen Muir, RN, MSN, CNS "DBA Nurse"
1-877-DBA-NURSe/ 1-877-322-6877
emuir@nshs.edu
Happy Thanksgiving!
As we give thanks
for all the blessings in
our lives, the
Diamond Blackfan
Anemia Foundation is
mindful and grateful
to the many families
and friends that
support our mission
with their generous donations and fundraising efforts.
Our accomplishments are because of your
commitment. Thank you!
Wishing everyone a very Happy Thanksgiving!
Journal Club
It takes a village.
What? Hillary Rodham Clinton not your cup of tea? Perhaps you
feel her book was a socialist manifesto aimed at destroying the
American family, or, perhaps you question whether she wrote the
book atall (http://en.wikipedia.org/wiki/It_Takes_a_Village). Yes,
the previous reference w
as to Wikipedia... I have no shame.
Steven R. Ellis, PhD
Research Director
These controversies however, are
neither here nor there as far as this
month's Journal Club is concerned.
Instead, what I hope you can
appreciate is that sometimes groups
of individuals with diverse skills,
when joining together to work as
one, can accomplish more than each
member of the group working
independently.
Such a group, led by Jason Farrar and David Bodine, recently
published a manuscript in Blood entitled, "Ribosomal protein
deletions in Diamond Blackfan anemia." This interdisciplinary
group consisted of physicians, genome scientists, and a
ribosomologist. Their goal was to identify genes affected in DBA
patients whose genes had not been identified by traditional DNA
sequencing methodologies. The approach they employed was to
scan the entire genome of these patients for lost genetic
information focusing on ribosomal protein genes that may have
been deleted.
Before discussing the results of this study, let me first briefly
review gene discovery in DBA. As most of you are aware, the first
DBA gene was identified by a group led by Niklas Dahl in
Sweden. This group identified a DBA patient that had a
chromosome translocation where chromosomes are broken and
fused to one another in an abnormal fashion1. The genes present at
these translocation breakpoints are typically thought to play a role
in the diseases where such translocations occur, which was indeed
the case for DBA. In looking at the RPS19 genes in other DBA
patients, it was found that several others had mutations predicted to
inactivate the Rps19 protein. Thus, we had our first DBA gene,
which is now known to be mutated in approximately 20-25% of
DBA patients2. Through the efforts of Dr. Hanna Gazda in Boston
and the DBA Registry in New York, a second DBA gene, RPS24,
was identified, and it too encoded a ribosomal protein 3. A total of
9 DBA genes have now been identified, all of which encode
ribosomal proteins. Together these nine genes account for the
genes affected in a little over 50% of DBA patients. These genes
were largely identified by DNA sequencing and the identification
of potential disease causing mutations. Despite these successes,
several large scale DNA sequencing efforts have been carried out
in DBA patients and still there are many patients whose genes have
yet to be identified.
One explanation for the failure to identify genes affected in the
remaining patients is that, perhaps for these patients, the mutations
are in one of the tens of thousands of other genes in the human
genome that do not encode ribosomal proteins. This is a formal
possibility and one that will likely be explored in a subsequent
Journal Club. The other possibility is that, in some of these
patients, the ribosomal protein gene affected may be completely
deleted. Since DNA sequencing requires that a gene be present for
it to be sequenced, sequencing a patient's DNA where one of two
ribosomal protein genes is completely missing would just give you
the sequence of the remaining normal gene, which would
appear....well, normal, and so be missed.
So, to address this possibility Farrar et al used SNP-Array
genotyping and comparative genome hybridization (CGH) to look
for regions of patients' genomes where genetic information was
lost. These are amazing technologies where the entire genome can
be scanned with enough sensitivity to pick up a change from two
copies of a gene to one, and so it is ideally suited for looking for
ribosomal protein deletions in DBA patients. Of the 51 patients
analyzed in this fashion, 9 were shown to have deletions in known
DBA genes including RPS19, RPS17, RPS26 and RPL35A. These
results close in on the ultimate goal of identifying each of the
genes affected in all DBA patients.
Although no new genes were identified in this study, there were
some unexpected outcomes that have important implications. The
first is that some of the patients harboring these deletions exhibited
what is known as mosaicism, suggesting that not every cell
analyzed harbors the deletion. Interestingly, there was a correlation
between mosiacism and spontaneous remission. One could
envision in patients exhibiting such mosaicism mixtures of
apparently normal and mutant cells whose relative proportions
exhibit a dynamic behavior, the balance of which may determine
disease or remission. These studies provide the first molecular
insight into this very important phenomenon. The other
unanticipated finding related to RPS17, a previously characterized
DBA gene. In carefully analyzing the genome data, it was
determined that there were four rather than two copies of the
RPS17 genes in the human genome. This observation had not been
made before and raised the question as to whether or not RPS17
could really be classified as a DBA gene. This issue comes up
since previous reports on RPS17 inferred that a mutation would
reduce the amount of functional protein by 50%. But with 4 copies
present a mutation in one copy may not be enough to disrupt
function and trigger disease. Some of this same ambiguity
regarding the number of deleted genes was also evident in the
deletion analysis. This ambiguity was resolved by the
demonstration that those patients harboring the deletions did in fact
have defects in ribosome synthesis indicating a functional
consequence of the gene deletion. Consequently, despite the
realization that there are 4 copies of RPS17 in the human genome,
we can say with restored confidence that RPS17 is a DBA gene.
So what of the remaining patients whose genes remain to be
identified? I certainly think it is possible that more genes may be
identified by sifting through the tremendous amount of data that
comes from a whole genome analyses such as reported here. It is
also possible that smaller deletions may have been overlooked and
still more sensitive technologies may be needed. Or it may be
necessary to expand our reach beyond the ribosomal protein genes,
searching for the proverbial needle (mutation) in a haystack (tens
of thousands of genes) by examining whole genomes at the DNA
sequence level. Is this feasible? Yes, with technological
advancements in genome science coming at a breakneck pace,
approaches unheard of just a few years ago are now within reach.
So let us end by coming around full circle. As these technologies
advance and require specialized centers and highly trained
individuals, progress will more than ever require diverse groups of
individuals working together toward a common goal.
1. Draptchinskaia N, Gustavsson P, Andersson B, et al. The gene
encoding ribosomal protein S19 is mutated in Diamond-Blackfan
anaemia. Nat Genet. 1999;21:169-175.
2. Boria I, Garelli E, Gazda HT, et al. The ribosomal basis of
Diamond-Blackfan Anemia: mutation and database update. Hum
Mutat;31:1269-1279.
3. Gazda HT, Grabowska A, Merida-Long LB, et al. Ribosomal
protein S24 gene is mutated in Diamond-Blackfan anemia. Am J
Hum Genet. 2006;79:1110-1118.