June 2016  ●   Issue 20




Statement from the Newcastle coordination office on the outcome of the British EU referendum

While the outcome of the British EU referendum makes 24th June a sad day for the RD-Connect coordination team based at the JWMDRC in Newcastle, for research and education in the UK and for British patients with rare diseases, we would like to reassure our friends, colleagues and rare disease patients that this has no impact for RD-Connect in the foreseeable future.

The team in Newcastle is a multinational one and we are passionate about the benefits of international collaboration, particularly in rare disease. The referendum outcome is therefore something that we feel very deeply at a personal level. We are very much aware how many of our successes in Newcastle over the past 10 years were and are based on fruitful and enjoyable collaborations with colleagues from all the EU member states.

Many of our translational research projects have been directly funded either by the European Union or by patient organisations from EU countries. We highly value our collaborations with centres in the EU, which have resulted in an improved understanding of rare diseases, more accurate diagnoses and better care for patients across the EU. Beside these achievements, other very important outcomes of our collaborative projects have been the establishment of trust, respect and friendships among people working together.

The outcome of the British EU referendum will not affect these accomplishments and it goes without saying that we will continue to work together across borders.

In particular, for RD-Connect, nothing will change in the immediate period. Although there is not yet a plan or terms of negotiation set out by the Leave politicians, our understanding is that the process of leaving will take at least 2 years. In that time, as far as we know the UK will still be participants in programmes such as FP7 and Horizon 2020. Therefore, the coordination office of RD-Connect will continue supporting rare disease research for the near future. It is our hope and expectation that negotiations will enable this to continue even in the event that the UK does complete the leaving process, but one good thing about EU-wide collaborations like RD-Connect is that it will still continue as a project no matter what!

~ The RD-Connect Newcastle Team


European Reference Networks will facilitate cross-border healthcare and research on rare diseases

2016 is a breakthrough year for European rare disease communities. The European Commission launched European Reference Networks (ERN) to integrate the existing European networks for rare diseases and facilitate the formation of new ones.

International networks allow experts from across Europe to unite their efforts to tackle rare diseases. ERNs’ primary interest is to improve care and make patients’ lives better. By bringing together healthcare and research, ERNs facilitate development of new therapies. They also harmonize care standards and increase equity of health provision across EU Member States.

The ERNs are organised into higher-order categories, such as Rare Bone Diseases, Rare Eye Diseases (see the full list), which will allow including also the rarest - and often neglected – diseases that lack proper networks. Thanks to continuous funding from the European Commission, ERNs will support research and patient care in a sustainable way.

Many RD-Connect partners are deeply engaged in this process and are partners or coordinators of some of the proposed ERNs. This includes the John Walton Muscular Dystrophy Research Centre in Newcastle and the coordinators of our partner projects NeurOmics and EURenOmics, who have submitted applications to create ERNs for rare neuromuscular, neurological and kidney diseases respectively. Each network would unite numerous healthcare providers (centres of expertise) and research centres from several European countries to improve health outcomes of patients with rare and ultra-rare diseases. In contrast to already existing European networks, ERNs would focus on a wide range of diseases - both genetic and acquired - and create a foundation for providing best practice care and diagnosis for patients at a national level. 

ERNs will foster translational research, and the research activities of the approved ERN applications will be a key element in their success. The expert centres that make up the networks are actively engaged not only in care for patients with rare diseases but also in research into better diagnosis, management and therapies, and linking ERNs' healthcare goals with research will be of direct benefit to patients. In particular, the use of next-generation sequencing technologies will become increasingly important for diagnosis of patients seen by ERN centres and for translational research towards therapies. RD-Connect engaged with all prospective ERN coordinators to offer the benefits of the RD-Connect genomics platform for analysis of sequencing data and of RD-Connect tools and services for patient registration and biobanking. ERN centres can securely share sequencing data from all patients who have consented to have their data shared for research purposes and analyse these patients against other individuals not only from their own cohorts but also from all the other cohorts submitted to the system. This will be of particular interest for patients without a genetic diagnosis, since it aids in gene discovery and finding confirmatory cases, and collaboration with RD-Connect to facilitate research towards diagnosis of the undiagnosed patients in each ERN.

As well as the genomic analysis platform, RD-Connect will support successful ERNs in ensuring phenotypic data collected is amenable for reuse for research in line with FAIR (findable accessible interoperable and reusable) data principles and providing assistance with biobanking activities to enable samples collected within the ERN remit to be stored and made accessible for future research use. Support with ethical and consent issues is available from our ELSI team.

More information is available on the ERN website and the RD-Action website.

 ~ Dorota Badowska and Rachel Thompson, Newcastle University


2016 BBMRI-LPC Whole Exome Sequencing Call

Sequencing the exome of 500 rare disease samples in collaboration with EuroBioBank

BBMRI- LPC (Biobanking and Biomolecular Resources Research Infrastructure – Large Prospective Cohorts) is one of the largest biobanking networks in Europe aiming to facilitate scientists’ access to large prospective study sets on human health and disease. The 2016 BBMRI – LPC Whole Exome Sequencing (WES) Call is offering a unique opportunity to genetically diagnose rare disease patients with samples deposited in Biobanks from the EuroBioBank network.

The program will provide free-of-charge Whole Exome Sequencing (WES) and bioinformatics analysis for a total of 500 samples, including rare disease patients and their relatives, from 10-30 coordinated projects.

The sequencing and analysis will be carried out at the Centro Nacional de Análisis Genómico (CNAG-CRG) and at the Wellcome Trust Sanger Institute (WTSI).

CNAG-CRG is a genomics research platform based in Barcelona (Spain) that has the mission to carry out large scale projects in DNA sequencing and analysis in collaboration with researchers from Catalonia, Spain and from the international research community. The Wellcome Trust Sanger Institute is a world leader in genome research and aims to deliver new insights into human and pathogen biology that change the course of biology and medicine. Our mission is to use genome sequences to increase understanding of human and pathogen biology in order to improve human health.

With this call BBMRI-LPC wants to promote the utilization of cutting-edge next-generation sequencing technology for the identification of novel causative variants and genes and to molecularly diagnose rare disease patients. BBMRI-LPC also wants to promote biobanking for rare diseases, the use of rare diseases biobanks and responsible data sharing.

The "informed consent" allows that anonimyzed samples and sequencing data and results are included in CNAG and WTSI's internal databases and distributed in secure controlled Access databases such as the European Genome-phenome Archive (EGA) and RD- Connect.

To apply, fill in the submission form. For more information, see the call guidelines.

Important dates:

• Call launch: June 23rd

• Project Submission deadline: July 25th

• Review Process deadline: August 31st

• Sample Submission deadline: September 30th

In case you need further information, please send an email to .


Report from European Conference on Rare Diseases and Orphan Products

This year’s EURORDIS Annual General Meeting and European Conference for Rare Diseases & Orphan Products (ECRD) were held on 26–28th May in Edinburgh. Both events were a great opportunity to meet colleagues from different Rare Disease Organisations and exchange ideas. The EURORDIS Annual General Meeting also provided an update and review of the year 2015, which was a very active year for EURORDIS.

The organisers arranged a number of tutorials before the main sessions, which focused on Game Changers for the diagnosis, understanding, management and treatment of rare diseases. The first tutorial, led by the European Medicines Agency (EMA), looked at EMA Regulatory Routes supporting Orphan Drugs. The second tutorial concerned Health Technology Assessment and ways to engage with health providers for rare diseases.

The tutorial that I attended showed how the RD-Connect Platform could support Rare Disease European Reference Networks (ERNs). In a series of discussions, Prof. Hanns Lochmüller, Dr Pauline McCormack and Dr Sergi Beltran presented an overview and the current status of the RD-Connect project, which holds various databases of value for ERN research aims. ERNs need to access information that has been stored in a correct manner in a system allowing interaction with investigators and data providers, including Patient Organisations. Therefore, the Platform’s ability to access databases, registries, biobanks and bioinformatics makes it a very useful tool. As explained during the workshop, appropriate consent has been obtained and the Patient and Ethics Council is effective in reviewing and addressing issues that may arise. Next, Sergi demonstrated that the system is now up and running, and the attendees (even inexperienced users like me) were able to work on a pilot area to see how effective the RD-Connect system is for genomic analysis, allowing users to find the precise causative mutation out of the thousands of areas where one person's genome differs from another.

Links to the presentations by the RD-Connect team given at ECRD2016 are available here.

~ Joseph Irwin, RD-Connect Scientific Advisory Board member and member of Spinal Muscular Atrophy Support UK


International PhD Course in Molecular Medicine at the Vita-Salute San Raffaele University

Applications are now open for the International PhD Course in Molecular Medicine academic year 2016-2017 at the Vita-Salute San Raffaele University in Milan. The three-years course offers an educational programme for young PhD students to help them find a position in the national and international academic and industrial bodies in the field of research.

The Course includes PhD fellowships at San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), in the Cellular and Molecular Physiopathology and Basic and Applied Immunology and Oncology.

Application deadline: 18th July 2016. For more information visit the Course website.


Upcoming events


Summer School and Workshop on Rare Diseases at the Istituto Superiore di Sanità

This autumn, the National Centre for Rare Diseases (CNMR) of the Istituto Superiore di Sanità, Rome, Italy is organising two training events on rare disease registries:

• The 4th International Summer School on Rare Disease and Orphan Drug Registries (26-28 September 2016). The event is addressed to health professionals, researchers, clinicians and representatives of patient associations involved in establishing rare disease patient registries. Using the Problem-Based Learning methodology, we introduce the attendees to the aims and needs of clinical research registries.

• The RD-Connect BYOD (Bring Your Data) Workshop to Link Rare Disease Registries (29-30 September 2016). The workshop is a blend of a hackathon (an event where computer experts and other stakeholders work together on a software project) and a hands-on tutorial, where data owners generate their first own linked data and make them FAIR (Findable, Accessible, Interoperable and Reusable), which allows information exchange with other systems.

Important dates, additional information, updated programs and any updates on the events are available on the Institute’s website.

Registration is open until 10th of July 2016 and can be carried out for either one or both events via the online form.


3GbTest  and RD-Connect joint course on Next Generation Sequencing

3GbTest is organising a 4-day course on Next Generation Sequencing, taking place in Lisbon, Portugal on 24-27th October 2016. International speakers will elaborate on clinical diagnostics using exome/genome sequences, variant identification and analysis including afternoon practical sessions. The event will include a hands-on training session on the RD-Connect platform.
3GbTest was funded until Aug 2015 under EU FP7 and aimed at introducing whole genome sequence analysis technologies (3Gb-testing) into diagnostics of genetic diseases. The project continues to organise training workshops and courses.
For more details on the next course, visit the course website. The registration deadline is 24th September.


The 9th European Huntington´s Disease Network (EHDN) Plenary Meeting in The Hague

The 9th Plenary Meeting of te European Huntington´s Disease Network (EHDN) will take place at the World Forum in The Hague, The Netherlands, 16-18 September 2016. The meeting will be held in conjunction with the 17th European Huntington´s Disease Association (EHA) Meeting. EHDN is one of the RD-Connect partners, and actively collaborates with the ID-Cards directory.

Topics presented during the EHDN Plenary Meeting will contain reports on recent advances in HD research (in both basic and clinical sciences). Aside from participating in the plenary and other parallel sessions, attendees will also have the opportunity to meet experts in the field of HD studies in more informal settings.

The program adressed for both scientific as well as lay audience, includes presentations, posters, updates on clinical trials, teaching courses and the EHDN business meeting.

Registration for the EHDN Plenary Meeting 2016 will be open until 31st of July, 2016.
More details are available at he .


Past events


RD-Connect hackathon on rare disease registries and biobanks

At the beginning of June, RD-Connect held a hackathon to improve the layout for the RD-Connect ID-Cards directory tool. Developers, users and data managers from six RD-Connect partner organizations (Fondazione Telethon, University Medical Center Groningen, Medical University of Graz, Istituto Superiore di Sanità, Karolinska Institutet, BBMRI-ERIC) gathered in Graz to work together on expanding ID-Cards functionalities and improving its usability.

RD-Connect ID-Cards is an online directory of rare diseases registries and biobanks worldwide. It lets patients and researchers find registries or biobanks dealing with the rare disease of interest and provides general information and metadata collected in their databases. ID-Cards is also the portal where biobanks can apply to join RD-Connect.

To improve the RD-Connect ID-Cards 2.0 directory interface, the participants discussed how to:

• better display the disease matrix associated with each registry or biobank

• simplify the filling of requested fields by biobank’s and registry’s managers

• improve the search function

• facilitate navigation from the from the ID-Cards to RD-Connect Sample Catalogue

Taking advantage of being hosted at the BBMRI-ERIC headquarters - the heart of European biobanking - the organizers launched a discussion to integrate the RD-Connect ID-Cards with the BBMRI-ERIC Directory 2.0. It was agreed that integrating the two systems would ensure that data are always consistent and up-to-date. It would also help the Biobank managers to avoid inputting data twice. This integration represents a win-win strategy. On one hand, the wider outreach of BBMRI-ERIC ensures higher visibility to rare disease biobanks; and on the other hand, the Biobank assessment protocol developed by RD-Connect ensures the quality of data in the directory.

Next actions:

• Launch ID-Cards version 2.0

• Invite additional biobanks and rare diseases registries to be included in the RD-Connect ID-Cards

• Develop ID-Cards as a FAIR data point (making data more Findable, Accessible, Interoperable and Reusable)

• Link RD-Connect ID-Cards 2.0 with the BBMRI-ERIC Directory 2.0

~Stefano  Benvenuti, Fondazione Telethon



Featured publications 




Overview of existing initiatives to develop and improve access and data sharing in rare disease registries and biobanks worldwide

López Martin E, et al., (2016)
Expert Opinion on Orphan Drugs

This article is an overview of existing initiatives that facilitate access to rare disease patient registries and biobanks, future challenges of accessing data/biosamples and the major barriers to achieve interoperability and worldwide data sharing. It has been recently published in “Expert Opinion on Orphan Drugs”, a relatively new international journal (launched in 2013) that covers all aspects related to treatments for rare diseases. As the topics covered in this review are of enormous importance, the dissemination of this information throughout rare disease professionals who perhaps may not know much about it, has been considered highly relevant.

Rare diseases patient registries and biobanks are highlighted as essential tools for surveillance, as well as for providing the basis for research and policy decisions. However, this article also shows that there is still little access to data and important limitations regarding interoperability between these resources. The project RD-Connect is outlined as one of the most important international strategies trying to address these limitations. In fact, the objective of this project is to enable cross-linking and efficient distribution of quality-controlled data to the rare disease research community in a secure ethical and legal framework. The participation of RD-Connect in the Matchmaker Exchange is also highlighted, since it ensures the interaction with other international teams and projects that also aim to facilitate the matching of cases with similar phenotypic and genotypic profiles.

~Estrella López Martin and Manuel Posada


Design, set-up and utility of the UK facioscapulohumeral muscular dystrophy patient registry

Evangelista T, el al., (2016)
Journal of Neurology

An article published in the Journal of Neurology describes the establishment of a UK registry for Facioscapulohumeral Dystrophy (FSHD) patients designed to collect information that may identify participants for clinical trials. The authors, focus on how the patient-initiated UK FSHD Registry has been invaluable in recruiting people to take part in research that will aid the development of future therapies.

Despite being one of the most common neuromuscular disorders, FSHD remains a rare inherited disease estimated to affect 1 in 15,000 people. Currently, no treatments exist which can halt or reverse the progression of FSHD. The development of such treatments has been hindered by difficulties in recruiting sufficient numbers of well-characterised patients, given the rarity of the condition. It is hoped that a national registry will help to overcome this hurdle.

Funded by Muscular Dystrophy UK and developed under the umbrella of the neuromuscular network TREAT-NMD, the UK FSHD patient registry contains large amounts of accurate information from 640 FSHD patients. A significant cohort of patients are interested and able to participate in future clinical research, with the registry already enabling the John Walton Muscular Dystrophy Research Centre to recruit 70% more participants than would have been possible through local contacts alone.

By asking patients to provide the majority of their data through electronic communication, it has been possible to identify a large number of patients with FSHD in the UK in a short time frame and with limited resources. The UK registry has also aided the recruitment of patients for a natural history study of infantile-onset FSHD, with the longitudinal analysis of patient-related outcomes expected to provide much-needed baseline information for future trials.

It is now hoped that an internationally-agreed core dataset will enable the establishment of a ‘Global FSHD registry’, instrumental in sharing and exploiting data globally to advance the research and development of treatments, therapies and care for all those diagnosed with FSHD.


Co-expression of phenylalanine hydroxylase variants and effects of interallelic complementation on in vitro enzyme activity and genotype-phenotype correlation

Shen N, et al., (2016)
Molecular Genetics and Metabolism

In phenylketonuria patients, the phenylalanine hydroxylase (PAH) enzyme activity levels depend on the combination of different of PAH mutations. In some heterozygous patients with a particular combination of PAH mutations, symptoms may differ from the expected ones, possibly due to genetic interactions the PAH variants.

The authors investigated the co-expression of PAH alleles reported in patients with inconsistent phenotypes. The researchers used cell cultures to measure the activity of 17 different PAH variants and compared the results with the outcomes predicted based on phenylketonuria online databases.

The data showed that two different PAH variants could interfere with each other both positively or negatively. For example, one of the variants could have a dominating influence on PAH activity in cells. In some cases however, researchers found inconsistencies between cell cultures and patients, e.g. only mild reductions of PAH an patients despite of dramatic reductions in cell cultures.
However, in some cases cells showed different levels of PAH activity than the patients carrying the same PAH variant combination.

This work, performed within the RD-Connect project, contributes to the understanding of how different genetic variants can interact with each other and determine the intensity and types of symptoms in the patients.


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