November 2014  ●   Issue 9


Publication highlights

Over 150 publications, including review and basic scientific research articles, have been generated by RD-Connect, NeurOmics and EURenOmics in recent months. Such articles not only highlight the important outputs and impact the three projects are having within the rare disease community but also demonstrate the breadth and range of scientific expertise each of the projects have. A summary of recent publications is listed below. Further details are available on each of the project websites.


 • A review article that discusses the impact of omics technologies for patients with rare diseases has been published in this month's Expert Opinion on Orphan Drugs. This review begins with an overview of the omics fields of relevance - genomics, transcriptomics, proteomics, metabolomics and pharmacogenomics - for rare disease. This is followed by a discussion of the challenges that remain in maximising the potential of these technologies and translating them to clinical benefit, particularly the requirement for large-scale collaboration and data sharing.

• As highlighted in last month's newsletter, RD-Connect partners Mascalzoni et al., 2014 published an international charter of principles for sharing biospecimens and data in last month’s European Journal of Human Genetics. This landmark publication contains a template for both material transfer agreements (MTA) and Data Transfer Agreements (DTA) both of which are available to download on the updated Ethics, Social and Legal Issues (ELSI) section of the RD-Connect website.

• A full list of RD-Connect related publications is available here.


• Herrmann et al., 2014 recently published a research paper in The American Journal of Human Genetics. Whole genome sequencing of members from two separate families was used to identify heterozygous missense mutilations in the CRB-binding domain of the gene that encodes Synaptotagmin-2 (SYT2 C2B), a protein that functions as a calcium sensor for neurotransmission. Identification of such mutations in the SYT2 C2B domain represent an important cause of presynaptic congenital myasthenic syndromes and link them with hereditary motor axonopathies.

• In a research article published in The American Journal of Human Genetics, Cottenie et al., 2014 used whole exome sequencing to identify heterozygous compound mutations in the gene that codes for the immunoglobulin-helicase-µ-binding protein 2 (IGHMBP2) in patients with recessive Charcot-Marie Tooth disease Type 2 (CMT2). Interestingly, this was an unexpected finding as IGHMBP2 is more commonly associated with spinal muscular atrophy with respiratory distress (SMARD1). Mutations in CMT2 were predicted to be less aggressive as compared to those in SMARD1. Further fibroblast and lymphoblast studies indicated that the IGHMBP2 protein levels are significantly higher in CMT2 than SMARD1, but lower than controls, suggesting that the clinical phenotype differences are related to the IGHMBP2 protein levels.

A full list of NeurOmics related publications is available here.


• Published in the New England Journal of Medicine, Klootwijk et al., 2014 described the identification of a heterozygous missense mutation in the EHHADH gene, which codes for an enzyme that is involved in peroxisomal oxidation of fatty acids and is expressed in the proximal tubule of the kidney, in individuals with isolated autosomal Fanconi's syndrome. It is believed that the EHHADH gene mutation creates a new mitochondrial targeting motif which in turn leads to defective mitochondrial metabolism and therefore Fanconi's syndrome. 

Devuyst et al., 2014 recently published a review article in The Lancet, which discusses the challenges, opportunities, and perspectives in rare inherited kidney diseases. This was produced in collaboration with the Board for Inherited Kidney Diseases of the European Renal Association and Dialysis and Transplant Association.

A full list of EURenOmics related publications is available here.


Report from the 21st EURORDIS Round Table of Companies (ERTC) meting, Barcelona, Spain.

Initiated in 2004, the EURORDIS Round Table of Companies (ERTC), is a “club” of pharmaceutical companies with a common interest in rare diseases and orphan drug development. The 21st ERTC was an occasion to review and discuss issues around collecting, registering and sharing patient data in order to foster the development of treatments for rare diseases. There were 80 participants from 14 different countries attending this meeting, which looked at ongoing challenges in sharing rare disease patient data.

A need for cultural change

While progress has been made in the area of patient registries and data – notably through the adoption of the basic principles delineated in the EUCERD Recommendations on Rare Disease Patient Registration and Data Collection and the upcoming establishment of the European Platform of Rare Diseases Registration, which will also subscribe to these principles – there is still a need for cultural change. As Hanns Lochmüller, coordinator of  RD-Connect pointed out, “While competition between different research groups and drug development companies is a driving force to advance science and innovation, harmonisation and sharing of data is ultimately required to compare, combine and make best use of the results. This is especially true in rare diseases, where individuals with the conditions may be scattered across the world”.

Other outstanding issues also remain: Technically, the collection and sharing of patient data represents a major challenge: how to create interoperability between geographically and structurally dispersed entities and ‘siloed’ sources of data? There are also legal challenges, particularly the anticipated impact of the proposed European legislation on data protection. Socially & ethically, it is still not completely understood how to achieve a comfortable balance for patients between sharing data and protecting privacy and confidentiality.

The European regulatory framework for data protection

In 2012, the European Commission proposed a major reform of the EU legal framework on the protection of personal data to incorporate considerations brought into play by the introduction of new technologies. The new legislation favours a high standard of protection of personal data that is widely considered detrimental to research. In particular, for health and medical research, the issue of “consent” remains critical. Many patients and researchers alike were hoping for a “consent –mechanism” that would address all concerns around processing and re-use of data. The proposal for a Regulation is still undergoing the legislative process.

What do patients want?

According to results of the EPIRARE patient survey and ongoing patient consultation on data sharing in the RD Connect project, a majority of patients want to share their data in order to move forward knowledge, treatments and care for their conditions. However, within this context of general willingness, patients desire an active role in the establishment, design, operating, and governance of data collection programmes. Patients need to trust the data-sharing network and the purposes of the research projects, want to see a firm process for consent, and want to be kept informed of progress gathered from their data sharing. This is particularly true for initiatives such as RD Connect, which heighten the sensitivity of patient information by integrating genetic material and data. Furthermore, patients are in favour of a common European registry infrastructure as well as a uniform European legislative framework for rare disease patient registries.

Toward a public-private model

The ERTC provided the occasion to examine the feasibility of establishing public-private partnerships in patient data collection which could include collaboration between members of industry and the European Platform of Rare Diseases Registration to be set up at the Joint Research Centre (JRC) in Ispra Italy, rare disease Centers of Expertise, European Reference Networks, and academics through EU-funded research projects such as RD-Connect.

As a community, we can congratulate ourselves on coming a long way in building consensus around guiding and aspiring principles for collecting and sharing patient data to maximise opportunities for improved diagnosis and treatment development.

Many disease-specific communities – researchers, companies and patient groups - have demonstrated the translation of these principles into action. Yet for many others, this is not yet a reality,” observes Anna Kole, Registry and Biobanks Manager, EURORDIS.

We will continue this open dialogue on how to best build common incentive structures and effect a true cultural change in data sharing to ultimately deliver concrete benefits to patients.

-Anna Kole


European perspectives on ethical issues and policies in whole genome sequencing: invitation to participate in 3Gb-TEST survey 

As part of a European project 3Gb-TEST, which focuses on diagnostic applications of whole-genome sequencing,  we are trying to gather European perspectives on ethical issues in WGS and information about recommendations and policies in place across Europe.  As the majority of studies to date have been largely centred around the USA and Canada this is a unique oppertunity to build up information about  European points of view and policies on these issues.

The use of whole genome sequencing for medical diagnosis:


Recommendations, policies, or issues with recommendations or policies that you have encountered:


Sharing anonymised case studies which highlight ethical issues:


Please visit the project website for further details.


RD-Connect gender action report  

To ensure that both men and women are equally represented in the RD-Connect a series of gender indicators were produced to measure progress towards gender equality within the project. Indicators were developed to measure the progress made with regards to recruitment, retention and career advancement, and also the progress achieved in policies, procedures and programmes which greatly influence the relative position of women and men. The basis for this report is a online questionnaire which was sent to all full RD-Connect partners. A total of 23 out of 27 partners completed the questionnaire. A summary of the results are as follows:

Gender balance within RD-Connect partner institutions

The questionnaire asked for details about the roles of women within partner institutes. Feedback indicated that women:

• are well represented within RD-Connect in administration and management positions. 

• are well represented in the PhD (67%), Scientist/Researcher (50%), post-Doctoral (64%) and Clinician (67%) categories.

• represent only 25% of the principal investigators. 

Gender policies and activities reported by RD-Connect partners

The questionaire also asked for feedback about the availability of policies and activities that can have an impact on gender equality within partner institutions. Feedback demonstrated that: 

• Maternity and paternity leave policies were generally available in all partner institutes. 

• Over half of the partner institutions have a child care policy, but only 9 provide access to childcare facilities. 

• Only 4 partner institutions reported providing staff with training in gender awareness. 

• A little over half of the partner institutions reported that they plan networking activities to raise girls’ interest in science and research. 

• A little over half of respondents reported that their organisation encourages gender sensitive behaviour to at least a moderate extent.

This exercise will be repeated 3 times during the course of the project and the results compared to measure progress.  The full gender action plan report will be shared among all partners and made publicly available via the RD-Connect website.

-Avril Palmeri


Upcoming events

For further information on future events please visit the events page on the RD-Connect website.

2nd International Rare Diseases Research Consortium (IRDiRC) Conference

7th-9th November, Shenzhen, China

IRDiRC is a global grouping of medical research funders, charities and pharma who have come together as a consortium to foster international collaboration and accelerate progress in rare disease research. Its goals are to deliver 200 new therapies for rare diseases and the means to diagnose most rare diseases by the year 2020. RD-Connect was one of the EU's first projects to be funded under the IRDiRC banner.

The 2nd IRDiRC conference aims to raise awareness of the topic of rare diseases around the world and to foster international collaborations involving Chinese researchers and clinicians. It will provide an unmissable opportunity to network with different rare disease communities from Europe, North and South America, Africa and Asia-Pacific. It is hoped that this will encourage and motivate investment of research and social resources in the field of rare diseases, to ultimately improve the diagnosis, treatment and care of patients and their families.

The following RD-Connect partners and associated partners have been confirmed as speakers during this three day event: Hugh Dawkins, Ségolène Aymé, Mathew Bellgard, Kym Boycott, Yaffa Rubinstein, Steve Groft, Yann LeCam and Michael Brudno.

Further information can be found on the conference website

III International EPIRARE workshop - Rare disease and orphan drug registries

24th-25th November, Rome, Italy

Patient registries are key tools in rare disease research and are now the subject of unprecedented popularity in translational research and of extensive policy actions. The III International EPIRARE workshop, organised by RD-Connect partner and registries work package leader Domenica Taruscio.

This workshop will cover the following topics: 

• the contribution of registration activities to recent advancements in the natural history, epidemiology and pathogenesis of rare diseases as well as patient care and quality of life.

• practical and innovative applications of registries, such as recruitment of patients in clinical trials, social and health service planning, patients’ support networks and integration with other initiatives, such as biobanks and databases for genomic and phenomic analysis.

• lessons learned in the management of rare disease registries, e.g. regarding financial sustainability, quality assurance, ethical issues and patients’ confidence, data protection, ownership and accessibility, as well as patients’ contribution, involvement and advocacy initiatives.

• the impact of e-health initiatives, new communication technologies and social networks.

• increasing the visibility of RD patient registries and databases within and beyond the scientific community and promoting the debate and the interaction among the many stakeholders of patient registration activities.

Further information can be found on the workshop homepage.


Why did I get this email?

You received this email because you are associated with RD-Connect, EURenOmics or Neuromics or because you signed up online. We will send out around one email per month with news of relevance to these projects and to IRDiRC. If you don't want to receive any further newsletters, you can unsubscribe using the link below. If you're reading this online or if it was forwarded by a friend, you can sign up to future editions here.