July 2016  ●   Issue 21




Next Cross-Project Annual Meeting in Berlin, 1st - 5th May 2017

The next RD-Connect Annual Meeting will take place in Berlin from the 1st till the 3rd of May 2017 and will be held back-to-back with the joint NeurOmics and EURenOmics final meeting, scheduled for the 4th and 5th of May.

On Wednesday 3rd of May the three projects plan a joint dissemination and impact day. The day will include sessions dedicated to policy, patient engagement and industry to help demonstrate the successes of the projects. The invited guests will include key politicians, patients, pharma companies and other stakeholders in the rare disease field.

We hope that many of you can join us for the Impact day on the 3rd May 2017 and we look forward to seeing you there!

Berliner Fernsehturm, public domain


The 6th Advanced RNA-seq data analysis course in Leiden

RD-Connect partner Leiden University Medical Center (LUMC) and the Dutch Research School on Bioinformatics and Systems Biology (BioSB) are organizing the 6th edition of the successful "Advanced RNA-seq data analysis course". The three-days course consists of lectures and practicals. The course will take place in Leiden, the Netherlands on 26th-28th of September. Seats have been reserved for participants from RD-Connect and associated projects until 31st of August.

The course is addressed for PhD students and post-docs with hands-on experience in Next Generation Sequencing as well as for scientific programmers and data analysts with a background in biology and bioinformatics. The basic knowledge of R and experience in running R scripts are required to participate in the course.

More information on the course and registration are available on the course website.


Postdoctoral position in systems genetics, University Medical Center Groningen

The Systems Genetics group at the Department of Genetics at the University Medical Center Groningen, the Netherlands, has opened several postdoctoral positions. The Department studies genetic and environmental risk factors for diseases, with a special focus on common complex diseases.

The team of Prof. Morris Swertz seeks a postdoc to work on Next Generation Sequencing data analysis at the crossroads between clinical diagnostic work and research. The project will focus on novel pipelines and methods to enable whole-genome interpretation, automated analysis/re-analysis, and population-based ‘big data’ methods to predict health/disease outcomes.

For more details, click here.


Research positions at the Institute of Genetic Medicine at the Newcastle University

The group of Dr Rita Horvath at the John Walton Muscular Dystrophy Research Centre in Newcastle seeks a Research Associate and a Research Technician to join a three-years project on genetics of rare neuromuscular diseases. The focus of the study are the disease mechanism of a rare group of severe childhood-onset neuromuscular diseases caused by abnormal RNA metabolism due to mutations in exosomal proteins.

Details on the vacancies are available on the website of the Newcastle University: Research Associate, Research Technician.


Featured publications 


Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia

Schlingmann KP, et al., (2016)
Journal of the American Society of Nephrology

High calcium in newborns – discovery of novel cause benefits children who may now be treated

A small number of newborns suffer from abnormally high calcium levels - a rare disease called idiopathic infantile hypercalcemia (IIH) - which can make them severely unwell . In recent years, hyperactivity of the enzyme activating Vitamin D has been identified as one cause of IIH. There is little specific treatment for this Vitamin D hyperactivity, except for omitting the recommended prophylactic Vitamin D and restricting calcium intake. Researchers from Münster, Germany, in collaboration with EURenOmics, have now identified disease mechanism causing IIH. Genetic studies on consanguineous families with IIH pinpointed the SLC34A1 gene as a promising candidate. SLC34A1 encodes a protein channel for sodium and phosphate that is needed in kidney to reclaim phosphate from the primary urine into the blood. Different animal models confirmed that phosphate wasting results in inappropriate activation of Vitamin D and is essential for the secondary development of high calcium levels. High phosphate diets, on the other hand, could restore normal phosphate, Vitamin D and calcium levels. Therefore, treatment of affected infants with phosphate supplementation is a novel, promising opportunity with few anticipated side effects and low cost. Newborns with IIH should therefore undergo investigation of their phosphate metabolism, while genetic analysis may help to identify children who will benefit from phosphate supplements.


Identification of mutations in the MYO9A gene in patients with congenital myasthenic syndrome

O'Connor E, et al., (2016)

Congenital myasthenic syndromes are a group of genetically diverse rare diseases caused by impaired structure and function of the neuromuscular junction. Typical symptoms include fatigable muscle weakness with a variety of accompanying features depending on the protein affected. In many patients diagnosed with congenital myasthenic syndrome, the causative gene is unknown. To identify genetic causation in a cohort of congenital myasthenic syndrome patients, the authors analysed their whole exome sequences. In a Kurdish and a German family, they found a mutation in the MYO9A gene, which encodes an unconventional myosin. Further experiments in cell cultures and in zebrafish suggest that MYO9A plays an important role in neuronal branching, axon guidance and formation of the neuromuscular junction during development, and is required for normal motor activity. The authors believe that MYO9A deficiency may affect the presynaptic motor axon and leads to congenital myasthenic syndrome.

The results highlight that not only the traditional neuromuscular junction-specific proteins, but also the so-called unconventional myosins, should be considered as candidate genes for congenital myasthenic syndrome. The study also is an example of how across-borders projects allow for identifying candidate genes for rare diseases. This work was conducted within RD-Connect and in collaboration with NeurOmics. 


Improving the informed consent process in international collaborative rare disease research: effective consent for effective research

Gainotti S, el al., (2016)
European Journal of Human Genetics

Emerging genome sequencing technologies and increased international data sharing between scientists create new opportunities for rare disease research. However, they also challenge patient data protection. It is essential to find the best balance between facilitating research for development of new therapies and protecting patients' right to integrity. Obtaining patients’ consent needs to be coordinated between research centres worldwide and include the same core elements of consent. Therefore, the procedure needs to be planned carefully to address any potential ethical and legal hurdles that may arise in the future. Coordination of obtaining informed consent should to consider two situations:

• new research collections (biobanks and registries) for which information documents can be created according to current guidelines;

• established collections obtained without informed consent or with a consent not covering all core elements.

The article proposes a strategy to deal with consent in both situations. It demonstrates the example of RD-Connect consortia, where these principles are already applied. The established principles, lessons learned and implications for future research are directly relevant to other internationally collaborative rare-disease projects.


Summer holidays break


As the holiday season is upon us, the next issue of the RD-Connect newsletter will be released end of September 2016.

We would like to thank our partners for the hard work through the year and we wish all of you joyful and relaxing summer break !!!

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