Sharon Terry

• Master of Arts
• CEO at Genetic Alliance

Introduction Pseudoxanthoma elasticum (PXE) is an autosomal recessive ectopic calcification disorder clinically affecting the skin, eyes, and vascular system. Most cases of PXE are caused by inactivating pathogenic variants in the ABCC6 gene encoding a hepatic transmembrane efflux transporter, which facilitates the extracellular release of ATP, the...

The ongoing debate on secondary use of health data for research has been renewed by the passage of comprehensive data privacy laws that shift control from institutions back to the individuals on whom the data was collected. Rights-based data privacy laws, while lauded by individuals, are viewed as problematic for the researcher due to the distribut...

Inorganic pyrophosphate (PPi) is a crucial extracellular mineralization regulator. Low plasma PPi concentrations underlie the soft tissue calcification present in several rare hereditary mineralization disorders as well as in more common conditions like chronic kidney disease and diabetes. Even though deregulated plasma PPi homeostasis is known to...

ABCC6 promotes ATP efflux from hepatocytes to bloodstream. ATP is metabolized to pyrophosphate, an inhibitor of ectopic calcification. Pathogenic variants of ABCC6 cause pseudoxanthoma elasticum, a highly variable recessive ectopic calcification disorder. Incomplete penetrance may initiate disease heterogeneity, hence symptoms may not, or different...

Pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI) are clinically distinct genetic entities of ectopic calcification associated with differentially reduced circulating levels of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Variants in ENPP1, the gene mutated in GACI, have not be...

Here, we argue that, in line with the dramatic increase in the collection, storage and curation of human genomic data for biomedical research, genomic data repositories and consortia have adopted governance frameworks to both enable wide access and protect against possible harms. However, the merits and limitations of di erent governance frameworks...

Human genomics is a translational field spanning research, clinical care, public health, and direct-to-consumer testing. However, law differs across these domains on issues including liability, consent, promoting quality of analysis and interpretation, and safeguarding privacy. Genomic activities crossing domains can thus encounter confusion and co...

Eric Lander, Françoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg and specialists from seven countries call for an international governance framework. Eric Lander, Françoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg and specialists from seven countries call for an international governance framework. Embryo culture dish used f...

Drawing on a landscape analysis of existing data-sharing initiatives, in-depth interviews with expert stakeholders, and public deliberations with community advisory panels across the U.S., we describe features of the evolving medical information commons (MIC). We identify participant-centricity and trustworthiness as the most important features of...

Electronic health records (EHRs) can be a major tool in the quest to decrease costs and timelines of clinical trial research, generate better evidence for clinical decision making, and advance health care. Over the past decade, EHRs have increasingly offered opportunities to speed up, streamline, and enhance clinical research. EHRs offer a wide ran...

Accurate clinical interpretation of children’s whole-genome and whole-exome sequences relies on comparing the patient’s linked genomic and phenotypic data with variant reference databases of both healthy and affected patients. The robustness of such comparisons, in turn, is made possible by sharing pediatric genomic and associated clinical data. De...

Background: Governments, funding bodies, institutions, and publishers have developed a number of strategies to encourage researchers to facilitate access to datasets. The rationale behind this approach is that this will bring a number of benefits and enable advances in healthcare and medicine by allowing the maximum returns from the investment in...

Drug discovery and development is commonly schematized as a "pipeline," and, although appreciated by drug developers to be a useful oversimplification, this cartology may perpetuate inaccurate notions of straightforwardness and is of minimal utility for process engineering to improve efficiency. To create a more granular schema, a group of drug dev...

Public health relies on technologies to produce and analyse data, as well as effectively develop and implement policies and practices. An example is the public health practice of epidemiology, which relies on computational technology to monitor the health status of populations, identify disadvantaged or at risk population groups and thereby inform...

Rare diseases collectively exert a global public health burden in the severity of their manifestations and the total number of people they afflict. For many patients, considerable barriers exist in terms of access to appropriate care, delayed diagnosis and limited or non-existing treatment options. Motivated by these challenges, the rare disease pa...

National and international public-private partnerships, consortia, and government initiatives are underway to collect and share genomic, personal, and healthcare data on a massive scale. Ideally, these efforts will contribute to the creation of a medical information commons (MIC), a comprehensive data resource that is widely available for both rese...

Due to the remarkable global surge in activity in rare diseases research over the last six years, including contributions by the International Rare Diseases Research Consortium (IRDiRC), the Consortium's 2020 goals have been largely achieved by 2017. Though these developments are gratifying, enormous challenges remain. With this paradox in mind, IR...

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder characterized by the mineralization of connective tissues in the body. Primary manifestation of PXE occurs in the tissues of the skin, eyes, and cardiovascular system. PXE is primarily caused by mutations in the ABCC6 gene. The ABCC6 gene encodes the trans-membrane protein ABCC6, whi...

Pseudoxanthoma elasticum is a prototype of heritable ectopic mineralization disorders, with phenotypic overlap with generalized arterial calcification of infancy and arterial calcification due to CD73 deficiency. Recent observations have suggested that the reduced inorganic pyrophosphate/phosphate ratio is the cause of soft connective tissue minera...

Introduction: The PhenX Toolkit, an online resource of well-established measures of phenotypes and exposures, now has 16 new measures recommended for assessing rare genetic conditions. Materials and methods: These measures and their protocols were selected by a working group of domain experts with input from the scientific community. Results:...

Two U.S. national initiatives have stated emphatically that people will be, not patients, but partners in clinical research.

In recent years, policy makers, organizations, and individuals have advanced efforts to promote the culture and infrastructure needed to support the secure accessibility of health and health care data.³ For example, the companies that are part of the Pharmaceutical Research and Manufacturers of America have committed to sharing their data.⁴ The Int...

Biobanks are increasingly powerful tools used in translational research, and disease advocacy organizations (DAOs) are making their presence known as research drivers and partners. We examined DAO approaches to biobanking to inform how the enterprise of biobanking can grow and become even more impactful in human health. In this commentary, we outli...

Introduction: Individuals have a moral claim to be involved in the governance of their personal data. Individuals' rights include privacy, autonomy, and the ability to choose for themselves how they want to manage risk, consistent with their own personal values and life situations. The Fair Information Practices principles (FIPPs) offer a framewor...

Heritable ectopic mineralization disorders represent a phenotypically diverse group of conditions characterized by deposition of calcium phosphate complexes in soft connective tissues. The prototype of such conditions is pseudoxanthoma elasticum (PXE), and related conditions with overlapping clinical features include generalized arterial calcificat...

While the science of human genomics is often focused on odds and probability, most of us do not experience risk that way. I am a carrier of a mutation in ABCC6, as is my husband. Rather than experiencing the odds we would have children with the autosomal recessive condition pseudoxanthoma elasticum (25% each pregnancy) as an abstraction, our reali...

Precision or personalized medicine through clinical genome and exome sequencing has been described by some as a revolution that could transform healthcare delivery, yet it is currently used in only a small fraction of patients, principally for the diagnosis of suspected Mendelian conditions and for targeting cancer treatments. Given the burden of i...

Genetic tests can result in abundant data that must be managed, interpreted, and afforded the appropriate protections (McGuire et al., 2008). Because of the numerous potential uses of these data, ethical use requires engaged and representative governance and oversight. The movement to publish these data in large genomic databases to make it broadly...

No doubt can remain as to the growing importance of the patient’s voice in biomedical research and regulatory science after U.S. President Barack Obama clearly stated that people would not be treated as subjects in the Precision Medicine Initiative but would be partners in the process. He said

Whole genome and whole exome sequencing are increasingly useful diagnostic tools for novel monogenic conditions. In order to confirm diagnoses made using these technologies, genomic matchmaking - the matching of cases with similar phenotypic and/and genotypic profiles, to narrow the number of candidate genes or ascertain a condition's etiology with...

There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for “the needle in a haystack” to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual resear...

Genomic research has generated much new knowledge into mechanisms of human disease, with the potential to catalyze novel drug discovery and development, prenatal and neonatal screening, clinical pharmacogenomics, more sensitive risk prediction, and enhanced diagnostics. Genomic medicine, however, has been limited by critical evidence gaps, especial...

Table S1. Copy numbers of ABCC6, ABCC6P1, and ABCC6P2 mutations in PXE patients.

On January 30, 2015, I had the great honor of attending the President's announcement about the Precision Medicine Initiative in the East Room of the White House. Along with many hard-working, visionary luminaries in clinical science, informatics, advocacy, and policy, I listened with great enthusiasm to the fabulous announcement. It was clear from...

Single mutations in the ATP-binding cassette transporter (ABCC6) gene (OMIM 603234) are known to cause the rare autosomal recessive disease pseudoxanthoma elasticum (PXE). Recently, we have found that copy number variations (CNVs) in pseudogenes of the ABCC6 gene are quite common. The aim of this study was to investigate the frequency and possible...

Abstract Pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI) are heritable ectopic mineralization disorders. Most cases of PXE and many cases of GACI harbor mutations in the ABCC6 gene. There is no effective treatment for these disorders. We explored the potential efficacy of bisphosphonates to prevent ectopic ca...

Purpose: With the accelerated implementation of genomic medicine, health-care providers will depend heavily on professional guidelines and recommendations. Because genomics affects many diseases across the life span, no single professional group covers the entirety of this rapidly developing field. Methods: To pursue a discussion of the minimal...

Introduction: Pseudoxanthoma elasticum (PXE), a multisystem orphan disease, clinically affects the skin, the eyes, and the cardiovascular system with considerable morbidity and mortality. The clinical manifestations reflect the underlying pathology consisting of ectopic mineralization of peripheral connective tissues. Areas covered: The diagnost...