News

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-Sophei 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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Solve-RD Treatabolome Webinar on YouTube

Solve-RD Treatabolome Webinar on YouTube

Solve RD Treatabolome webinar  given by Leslie Matalonga (CNAG-CRG) on 18 November 2022 is now available online!

The Treatabolome DB provides information on gene and variant-specific treatments for rare diseases. Currently, it includes up to 180 treatments associated with more than 1000 distinct variants - mainly for neuromuscular disorders.

In this webinar,we

  • provided an overview on the Treatabolome DB,
  • explained how to use the information,
  • showed how to find a treatment for a specific genetic disease and
  • showed how new data is being included and how you can contribute.

First RDMM-Europe project published

First RDMM-Europe project published

Solve-RD partners Ana Töpf and Volker Straub (John Walton Muscular Dystrophy Research Centre), together with Conrad Weihl and collaborators (Department of Neurology, Washington University School) have published their joint project in Acta Neuropathologica: "Loss of function variants in DNAJB4 cause a myopathy with early respiratory failure". Conrad Weihl was one of the first scientists that received Seeding Grant funding from Solve-RD within the European Rare Disease Models & Mechanisms Network (RDMM-Europe) to validate a novel disease-causing gene identified by Ana Töpf and Volker Straub.

Weihl, C.C., Töpf, A., Bengoechea, R. et al. Loss of function variants in DNAJB4 cause a myopathy with early respiratory failure. Acta Neuropathol (2022). https://doi.org/10.1007/s00401-022-02510-8.

Solve-RD Webinar: The Treatabolome DB

Solve-RD Webinar: The Treatabolome DB

In the last two years, the Treatabolome project, a Solve-RD initiative, promoted the collection of evidence about gene and variant-specific treatments for rare diseases. The information, gathered by experts and published in systematic literature reviews, is now stored and accessible in the Treatabolome DB. Currently, the database includes up to 180 treatments associated with more than 1000 distinct variants - mainly for neuromuscular disorders. Records are completed with clinical information by using standard vocabularies such as HPO, Orphanet, OMIM, Mesh and Chebi. The project is open to new data submissions and collaborations.

This webinar is especially relevant for people involved in rare disease diagnostics & care (clinicians, geneticists, genetic counsellors, etc). We will:

  • provide an overview on the Treatabolome DB
  • explain how to use the information
  • show how to find a treatment for a specific genetic disease
  • show how new data is being included and how you can contribute
Date: Friday, 18 November 2022, 2pm CET
Speakers: Sergi Beltran, Alberto Corvo, Leslie Matalonga (all CNAG-CRG)