Author: Birte Zurek

RDMM-Europe project published!

RDMM-Europe project published!

Solve-RD partners Antonio Vitobello from the University Hospital Dijon-Bourgogne and Elke Bogaert & Bart Dermaut from Ghent University in Belgium were connected by our European Rare Disease Models & Mechanisms Network (RDMM-Europe) initiative. They received Seeding Grant funding to generate Drosophila models that support the validation of new SRSF1 variants identified in a cohort of patients with syndromic developmental disorder associated with intellectual disability. Their findings have now been accepted for publication in The American Journal of Human Genetics.

Elke Bogaert, Aurore Garde, Thierry Gautier et al. SRSF1 haploinsufficiency is responsible for a syndromic developmental disorder associated with intellectual disability. The American Journal of Human Genetics (2023). https://doi.org/10.1016/j.ajhg.2023.03.016

Solve-RD GPAP Webinar on YouTube

Solve-RD GPAP Webinar on YouTube

The Solve-RD webinar on the new graphical user interface of the RD-Connect Genome-Phenome Analysis Platform (GPAP)  given by Leslie Matalonga (CNAG-CRG) on 12 April 2023 is now available online via this link!

The webinar focuses on how to navigate through the platform and use some of the advanced new functionalities to (re)analyse cases, including cohort level analysis and the use of Matchmaker Exchange.

Solve-RD Public Symposium

Solve-RD Public Symposium

Public Symposium at the Solve-RD Final Meeting 2023: The Impact of Solve-RD on Research & Care of Rare Disease Patients

The Public Symposium is open to the entire human genetics and rare disease community in Europe and beyond. In addition to presentations on Solve-RD achievements, we are very happy to have two keynote speakers: Ines Thiele (University of Galway) will outline the way “Towards a personalised systems biomedical approach for the diagnosis of inherited metabolic diseases” and Timothy Yu (Boston Childrens Hospital and Harvard Medical School) will speak about “Hyperpersonalized therapies for the long tail of genetic disease”. The Public Symposium is going to conclude with a round table discussion on “The Future of Rare Disease Diagnostics in Europe”. A list of excellent panellists will discuss what needs to change in rare disease diagnostics, the challenges and bottlenecks to take the next steps as well as concrete solutions on national, local, European and global level.

Date: Wednesday, 26 April 2023 from 8:30-12:30 CEST, online

Registration: https://us02web.zoom.us/webinar/register/WN_M1qQIxIhTwa37xFgwiAxJQ

Download the full programme here.

Download the symposium brochure here.

 

Programme:

Towards the future of rare disease diagnostics
08.30 AM - 10.15 AM | Chair: Ana Rath & Gulcin Gumus

  • Keynote lecture: Towards a personalised systems biomedical approach for the diagnosis of inherited metabolic diseases
    Ines Thiele, University of Galway
  • Keynote Lecture: Hyperpersonalized therapies for the long tail of genetic disease
    Timothy Yu, Boston Childrens Hospital & Harvard Medical School
  • Looking further: Patient organizations and advancing RD research on diagnosis
    Gulcin Gumus, Eurordis
  • SOLVE-RD 2.0
    Olaf Riess, University of Tübingen

 

Impact of Solve-RD on research & care of rare disease patients
10.45 AM - 12.30 PM | Chair: Han Brunner & Holm Graessner

  • Key SOLVE-RD achievements
    Holm Graessner, University of Tübingen
  • Genomics reanalysis of a pan-European rare disease  resource yields >500 new diagnoses
    Alex Hoischen, Radboud UMC & Sergi Beltran, CNAG-CRG
  • Round Table: The future of rare disease diagnostics in Europe
    Simona Bellagambi, Eurordis Board of Directors & Uniamo | Daria Julkowska, INSERM | Christina Kyriakopoulou, European Commission, DG Research & Innovation | Milan Macek, Charles University Prague | Olaf Riess, University of Tübingen | Lisenka Vissers, Radboud UMC | Timothy Yu, Boston Childrens Hospital & Harvard Medical School

RD-Connect GPAP webinar

RD-Connect GPAP webinar

Solve-RD will host a webinar in April to showcase the completely new graphical user interface of the RD-Connect Genome-Phenome Analysis Platform (GPAP) that will be released on the 22th of March. The webinar will focus on how to navigate through the platform and use some of the advanced new functionalities to (re)analyse your Solve-RD cases, including cohort level analysis and the use of Matchmaker Exchange.

Time: Wednesday, 12 April 2023; 1-2 pm CEST

Speaker: Leslie Matalonga, Steven Laurie & Sergi Beltran (CNAG-CRG)

Registration: https://us02web.zoom.us/webinar/register/WN_c73ZGHCzSLizuN0l6Wsreg

Audience: All Solve-RD partners interested in analysing phenotypic and genomic data from the project. No prior experience analysing (filtering and prioritising) genomic data through the GPAP is required. Users will learn how to navigate through the new interface to filter and prioritise variants using common annotations and on-the-fly gene panels associated to diseases, phenotypes, and pathways (PanelApp, OMIM, ORDO, HPO, Reactome). They will also learn how to easily interpret genomic variants according to ACMG guidelines and how to use integrated tools such as Exomiser and Varsome to prioritise results. Furthermore, users will also learn how to use advanced features included in the system such as identifying other similar cases both internally, and around the world through the Matchmaker Exchange network and perform cohort level analyses.

Seeding Grant project received follow-up funding

Seeding Grant project received follow-up funding

Solve-RD Seeding Grant recipient Michela Ori successfully received competitive grant from the Telethon Foundation (Italy)

Michela Ori and her group at the Department of Biology, University of Pisa, Italy have received Seeding Grant funding via the Solve-RD Rare Disease Models & Mechanisms Network (RDMM-Europe) program in August 2020.

Based on preliminary data obtained with the Solve-RD Seeding Grant, Michela's lab has successfully applied for a competitive grant from the Italian Telethon Foundation. The project with the title "Modeling Pitt-Hopkins syndrome and new pathogenetic variants of TCF4 by gene editing: a step forward toward personalized medicine (acronim: HOPeFOR)" started in March 2023.

Solve-RD partner Antonio Vitobello from CHU Dijon who initially identified those novel gene variants in patients with facial dysmorphism and who was matched to Michela Ori's group via RDMM-Europe will be a collaborator in this project.

More info (in Italian) here.

 

New publication: reanalysis of 1,522 index cases from ERN-ITHACA

New publication: reanalysis of 1,522 index cases from ERN-ITHACA

Anne-Sophie Denommé-Pichon from CHU Dijon and colleagues from Solve-RD & ERN-ITHACA published "A Solve-RD ClinVar-based reanalysis of 1,522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing." in Genetics in Medicine.

Within the Solve-RD project, the ERN-ITHACA aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. In their recent paper they present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses and lessons learned.

Data from the first 3,576 exomes (1,522 probands and 2,054 relatives) collected from ERN-ITHACA was reanalyzed by the Solve-RD consortium by evaluating for the presence of SNV/indel already reported as (likely) pathogenic in ClinVar. Variants were filtered on frequency, genotype and mode of inheritance and reinterpreted.

They identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance or high frequency).

Anne-Sophie and colleagues conclude that the “ClinVar low-hanging fruit” analysis represents an effective, fast and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock.

First RDMM Seeding Grant project received follow-up funding

First Seeding Grant project received follow-up funding

Solve-RD Seeding Grant recipient Alessandro Sessa successfully obtained a competitive grant from the Telethon/CARIPLO alliance in Italy.

Alessandro Sessa and his group at the IRCCS Ospedale San Raffaele, Milano, Italy have received Seeding Grant funding in April 2021 to validate rare missense variants identified by Siddharth Banka at the Manchester Centre for Genomic Medicine, UK. Based on preliminary data generated with the Solve-RD funding Alessandro Sessa successfully applied for a competitive grant from the Telethon/CARIPLO alliance (Italy) to continue the analysis (250.000€/2 years). The call (the first of its kind) was in support of basic research projects focusing on the study of genes/gene families, proteins, and RNA molecules whose function is unknown in rare diseases of genetic and non-genetic origin.

Holm Graessner receives the EURORDIS European Rare Disease Leadership Award 2023

Holm Graessner receives the EURORDIS European Rare Disease Leadership Award 2023

Holm Graessner receives the EURORDIS European Rare Disease Leadership Award 2023!

This is really a great honour, not just for me but for my team and the people I collaborate with. The dominating feeling is appreciation and gratefulness to the people I am privileged to work with in the area of rare diseases. And there are many nice and fit persons I collaborate with.

This is how Holm Graessner describes his surprise and joy about the award.

Since 2012, EURORDIS-Rare Diseases Europe has organized the Black Pearl Awards. Goal of the event is to recognise the major achievements and outstanding commitment of patient advocates, patient organisations, policymakers, scientists, companies, and media who strive to make a difference for the rare disease community.

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