PXE International BioBank and Clinical Data Registry
OCTOBER 1, 2010
By Sharon Terry, Executive Director, PXE International
Now in its 15th year, the PXE International BioBank and Clinical Data Registry is the centralized sample repository and registry for pseudoxanthoma elasticum (PXE). It enables translational research and treatment discovery. It was founded in 1996 by PXE International and is the world´s first advocacy organization-owned and managed biobank and registry.1 It operates as part of the Genetic Alliance BioBank and Registry, a cooperative venture that is extensible and responsive to the needs of nonprofit disease advocacy organizations. The BioBank provides very low cost (free to the affected individuals) infrastructure for PXE International to engage in sophisticated, novel research collaborations with academia and industry to develop new diagnostics and therapeutics and to better understand and treat disease. The BioBank has its own Institutional Review Board that oversees it and its projects.
A biobank, or sample repository, is a place to store blood, DNA, tissue samples, cell lines, organs and any other biological specimen. The PXE International BioBank has tens of thousands of samples, including DNA, tissue from every organ in the body, full body donations postmortem, and many special samples such as eyes, urine, breast tumor tissue and so on.
A clinical data registry, sometimes just called a registry, is a storage place for medical and clinical information about individuals. The PXE International Clinical Data Registry ties the biological samples to the clinical record and stores self reported data (surveys and questionnaires), medical records (from any specialist), images (CT scans, MRIs and so on) and anything else that can be scanned or typed in.
The BioBank and Registry performs the following key functions:
- Provides clinical data collection system with customizable, web-based interface for participant data entry. Controlled SNOMED vocabulary and minimum data sets provide enhanced data mining opportunities. More than 3600 individuals affected by pseudoxanthoma elasticum (PXE) are registered.
- Provides online login for both individuals and for PXE International for ease of sample and data management.
- Provides state-of-the-art storage facility and systems for collection, processing, archiving and distributing biological samples. Has new technology backup systems so that there is never a failure to maintain storage.
- Provides training and mentoring to PXE International by experts in biobanking and templates for all necessary documents and protocols.
- Provides tools for PXE International to recruit participants to the BioBank, using state-of-the art methods that emphasize trust, privacy protections, data security, empowerment of participants and the member advocacy groups, and ongoing education.2
- Provides a robust and dynamic process for informed donor decision-making, leading to truly informed consent, tailored to specific uses of the samples and related information.
- Provides a robust data mining system for querying and visualizing donor statistics and samples for cohort development.
- Facilitates collaboration between PXE International, academic, government and industry partners.3
Frequently Asked Questions
Why did PXE International found the Biobank and Registry?
Early on, the leadership of PXE International recognized that the disease was not well characterized – no one understood it very well – and we wanted to speed up the process of understanding the disease and finding treatments for it by gathering all of the biological samples and clinical information we could find.3, 4
Weren´t there many collections of DNA and tissue samples in 1996, when the bank was founded? Why create another collection?
Yes, there were many small collections of patient samples, and even smaller collections of patient clinical data. These small collections are ‘underpowered´, meaning they are too small to draw conclusions. Large collections allow a better understanding of the disease, the mutations, and the gene function because information from many people is factored in.
Are there any other benefits to one large collection?
Yes. Another problem with many small collections is trying to figure out how often a sign or symptom or mutation occurs. If an individual´s DNA or clinical information is in multiple collections, then when we try to figure out how often something occurs, that individual is counted more than once. For example: Mary Nelson gives her DNA to the PXE International BioBank, and then also gives DNA to Dr. Smith. She has a unique mutation, one that has not been seen in anyone else. Both PXE International and Dr. Smith publish a paper on the mutation, and because the information is de-identified, the scientific community now thinks there are two people with this unique mutation. This example is not so important, but illustrates how important the issue is when we are dealing with thousands of people and questions such as who loses their vision and when, how fast does it progress, what about other signs and symptoms and so on. One collection is very powerful and it makes no scientific sense to maintain more than one.
Another major benefit is the ability to coordinate science. If two scientists come to us and ask to do the same experiment, we recommend they collaborate to save time and money and precious samples.
And finally, because we know about all of the research done with the samples, we report back to the donors about the activity in the BioBank and Registry and the aggregated results of the use of their samples.
Does the PXE International BioBank and Registry freely distribute samples?
Yes, the BioBank and Registry regularly sends sample around the world and shares clinical data. We are excited to share these important resources; and it energizes the individuals who have donated to know their samples and data are being used for important discoveries. We have never turned down a request for a sample.
Does this mean the PXE International BioBank and Registry is centralized and no other countries can participate?
No, not at all. We have sample collections in South Africa, Germany, Italy and Belgium and simply index those samples in the BioBank, leaving the physical samples in those countries for the use of the scientists there. As long as there is one central index, it doesn´t matter where the sample is located physically.
What do you think about starting other PXE sample repositories? Isn´t more better?
We think there are limited resources (money, time, energy and samples) in the PXE community, so duplicating this resource would be a great waste. The PXE International BioBank and Registry is the largest in the world, not only for pseudoxanthoma elasticum but for any rare disease. It is held up as a model for other genetic diseases5-10. Further, duplicate repositories would run into the problem described above – duplicate samples confusing the science.
Why not just collect biological samples? Why bother with clinical data?
Biological samples without clinical data are not very useful. Basic science projects can be done, but the real power in biomedical research lies in correlating the samples with the data – what signs and symptoms you exhibit, your lifestyle and environment and how that changes over time holds the key to real understanding.
What successes can you point to that result from the PXE International BioBank and Registry?
They are too numerous to detail in a short paper. They include:
- Research agenda setting and overall direction11
- Gene mapping and mutation detection12-21
- Animal models30
- Cell Studies31-37
- Specific organ manifestations38-40
- Pregnancy41, 42
- Hypothesis for mechanisms44, 45
- Ethical, legal and social issues2, 46-53
Are you still recruiting?
Yes. This is a living, longitudinal biobank and repository. To get started, click the button below.
PXE International BioBank and Registry Today!
1. Terry SF, Boyd CD. Researching the biology of PXE: partnering in the process. Am J Med Genet. Fall 2001;106(3):177-184.
2. Beskow LM, Botkin JR, Daly M, et al. Ethical issues in identifying and recruiting participants for familial genetic research. Am J Med Genet A. Nov 1 2004;130(4):424-431.
3. Lin AE, Terry SF, Lerner B, Anderson R, Irons M. Participation by clinical geneticists in genetic advocacy groups. Am J Med Genet A. May 15 2003;119(1):89-92.
4. Terry SF, Terry PF, Rauen KA, Uitto J, Bercovitch LG. Advocacy groups as research organizations: the PXE International example. Nat Rev Genet. Feb 2007;8(2):157-164.
5. Allen A. Who Owns My Disease. Mother Jones. November/December 2001.
6. Terry SF. Learning genetics. Health Aff (Millwood). Sep-Oct 2003;22(5):166-171.
7. Marshall E. Genetics. Patient advocate named co-inventor on patent for the PXE disease gene. Science. Aug 27 2004;305(5688):1226.
8. Pennisi E. Biomedical research. Patients help track down disease gene. Science. Jun 2 2000;288(5471):1565-1567.
9. Merz JF, Magnus D, Cho MK, Caplan AL. Protecting subjects' interests in genetics research. Am J Hum Genet. Apr 2002;70(4):965-971.
10. Stockdale A, Terry SF. Advocacy Groups and the New Genetics. In: Alper J, et al., eds. The Double-Edged Helix. First Edition ed. Baltimore: The Johns Hopkins Unversity Press; 2002:80 to 101.
11. Uitto J, Boyd CD, Lebwohl MG, Moshell AN, Rosenbloom J, Terry S. International Centennial Meeting on Pseudoxanthoma Elasticum: progress in PXE research. J Invest Dermatol. May 1998;110(5):840-842.
12. Le Saux O, Urban Z, Goring HH, et al. Pseudoxanthoma elasticum maps to an 820-kb region of the p13.1 region of chromosome 16. Genomics. Nov 15 1999;62(1):1-10.
13. Bergen AA, Plomp AS, Schuurman EJ, et al. Mutations in ABCC6 cause pseudoxanthoma elasticum. Nat Genet. Jun 2000;25(2):228-231.
14. Le Saux O, Urban Z, Tschuch C, et al. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet. Jun 2000;25(2):223-227.
15. Ringpfeil F, Lebwohl MG, Christiano AM, Uitto J. Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc Natl Acad Sci U S A. May 23 2000;97(11):6001-6006.
16. Le Saux O, Beck K, Sachsinger C, et al. A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum. Am J Hum Genet. Oct 2001;69(4):749-764.
17. Le Saux O, Martin L. [The molecular genetics of pseudoxanthoma elasticum]. Ann Dermatol Venereol. Sep 2001;128(8-9):943-946.
18. Le Saux O, Beck K, Sachsinger C, et al. Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa. Hum Genet. Oct 2002;111(4-5):331-338.
19. Gheduzzi D, Guidetti R, Anzivino C, et al. ABCC6 mutations in Italian families affected by pseudoxanthoma elasticum (PXE). Hum Mutat. Nov 2004;24(5):438-439.
20. Pfendner EG, Vanakker OM, Terry SF, et al. Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum. J Med Genet. Oct 2007;44(10):621-628.
21. Ramsay M, Greenberg T, Lombard Z, et al. Spectrum of genetic variation at the ABCC6 locus in South Africans: Pseudoxanthoma elasticum patients and healthy individuals. J Dermatol Sci. Jun 2009;54(3):198-204.
22. Byrne J, Edelson, V., Friedland, A., Terry, S.F., . Eyes on the Prize: Truthtelling about Genetic Testing. Washington, DC: Genetic Alliance 2007.
23. Shi Y, Terry SF, Terry PF, Bercovitch LG, Gerard GF. Development of a rapid, reliable genetic test for pseudoxanthoma elasticum. J Mol Diagn. Feb 2007;9(1):105-112.
24. Vanakker OM, Leroy BP, Coucke P, et al. Novel clinico-molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart. Hum Mutat. Jan 2008;29(1):205.
25. Sherer DW, Sapadin AN, Lebwohl MG. Pseudoxanthoma elasticum: an update. Dermatology. 1999;199(1):3-7.
26. Sherer DW, Bercovitch L, Lebwohl M. Pseudoxanthoma elasticum: significance of limited phenotypic expression in parents of affected offspring. J Am Acad Dermatol. Mar 2001;44(3):534-537.
27. Bercovitch L, Terry P. Pseudoxanthoma elasticum 2004. J Am Acad Dermatol. Jul 2004;51(1 Suppl):S13-14.
28. Vanakker OM, Martin L, Gheduzzi D, et al. Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity. J Invest Dermatol. Mar 2007;127(3):581-587.
29. Plomp AS, Bergen AA, Florijn RJ, et al. Pseudoxanthoma elasticum: Wide phenotypic variation in homozygotes and no signs in heterozygotes for the c.3775delT mutation in ABCC6. Genet Med. Dec 2009;11(12):852-858.
30. Beck K, Dang K, Boyd CD. The tissue distribution of murine Abcc6 (Mrp6) during embryogenesis indicates that the presence of Abcc6 in elastic tissues is not required for elastic fiber assembly. J Mol Histol. Mar 2005;36(3):167-170.
31. Gheduzzi D, Sammarco R, Quaglino D, et al. Extracutaneous ultrastructural alterations in pseudoxanthoma elasticum. Ultrastruct Pathol. Nov-Dec 2003;27(6):375-384.
32. Beck K, Hayashi K, Dang K, Hayashi M, Boyd CD. Analysis of ABCC6 (MRP6) in normal human tissues. Histochem Cell Biol. Jun 2005;123(4-5):517-528.
33. Gheduzzi D, Guerra D, Bochicchio B, et al. Heparan sulphate interacts with tropoelastin, with some tropoelastin peptides and is present in human dermis elastic fibers. Matrix Biol. Feb 2005;24(1):15-25.
34. Quaglino D, Sartor L, Garbisa S, et al. Dermal fibroblasts from pseudoxanthoma elasticum patients have raised MMP-2 degradative potential. Biochim Biophys Acta. Jun 30 2005;1741(1-2):42-47.
35. Le Saux O, Bunda S, VanWart CM, et al. Serum factors from pseudoxanthoma elasticum patients alter elastic fiber formation in vitro. J Invest Dermatol. Jul 2006;126(7):1497-1505.
36. Pasquali-Ronchetti I, Garcia-Fernandez MI, Boraldi F, et al. Oxidative stress in fibroblasts from patients with pseudoxanthoma elasticum: possible role in the pathogenesis of clinical manifestations. J Pathol. Jan 2006;208(1):54-61.
37. Gheduzzi D, Boraldi F, Annovi G, et al. Matrix Gla protein is involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients. Lab Invest. Oct 2007;87(10):998-1008.
38. Bercovitch RS, Januario JA, Terry SF, et al. Testicular microlithiasis in association with pseudoxanthoma elasticum. Radiology. Nov 2005;237(2):550-554.
39. Bercovitch L, Schepps B, Koelliker S, Magro C, Terry S, Lebwohl M. Mammographic findings in pseudoxanthoma elasticum. J Am Acad Dermatol. Mar 2003;48(3):359-366.
40. Lebwohl M, Lebwohl E, Bercovitch L. Prominent mental (chin) crease: a new sign of pseudoxanthoma elasticum. J Am Acad Dermatol. Apr 2003;48(4):620-622.
41. Gheduzzi D, Taparelli F, Quaglino D, Jr., et al. The placenta in pseudoxanthoma elasticum: clinical, structural and immunochemical study. Placenta. Jul 2001;22(6):580-590.
42. Bercovitch L, Leroux T, Terry S, Weinstock MA. Pregnancy and obstetrical outcomes in pseudoxanthoma elasticum. Br J Dermatol. Nov 2004;151(5):1011-1018.
43. Bercovitch L, Robinson-Bostom L, Terry S, Pasquali-Ronchetti I, Harrist T. Re: yellowish papules on flexural areas in a child. Pediatr Dermatol. Nov-Dec 2003;20(6):543-545; author reply 545.
44. Borst P, van de Wetering K, Schlingemann R. Does the absence of ABCC6 (multidrug resistance protein 6) in patients with Pseudoxanthoma elasticum prevent the liver from providing sufficient vitamin K to the periphery? Cell Cycle. Jun 1 2008;7(11):1575-1579.
45. Garcia-Fernandez MI, Gheduzzi D, Boraldi F, et al. Parameters of oxidative stress are present in the circulation of PXE patients. Biochim Biophys Acta. Jul-Aug 2008;1782(7-8):474-481.
46. Terry SF, Davidson, M.E. Meeting the Needs of Affected Individuals in the New Genetics Age. Exceptional Parent. Vol 2000.
47. Terry SF, Davidson ME. Empowering the public to be informed consumers of genetic technologies and services. Community Genet. 2000;3(3):148-150.
48. Beskow LM, Burke W, Merz JF, et al. Informed consent for population-based research involving genetics. Jama. Nov 14 2001;286(18):2315-2321.
49. Terry SF, Terry PF. A consumer perspective on informed consent and third-party issues. J Contin Educ Health Prof. Fall 2001;21(4):256-264.
50. Rothenberg KH, Terry SF. Human genetics. Before it's too late--addressing fear of genetic information. Science. Jul 12 2002;297(5579):196-197.
51. Terry SF. Genetic Alliance BioBank. 2008; http://www.biobank.org. Accessed 12/20/2008, 2008.
52. Terry SF, Bonhomme N, Scott J. Screening for Heritable Disorders in Children: Efficacy from a Family/Consumer Perspective. Washington, DC: HRSA, MCHB; 2009.
53. Terry SF, Terry PF. A consumer perspective on forensic DNA banking. J Law Med Ethics. Summer 2006;34(2):408-414.