The first Solve-RD report confirms the benefit of an exceptional European research project focusing on rare diseases

More than 300 experts from 15 countries, including clinical practitioners, geneticists, patient representatives and researchers, are taking part in the Solve-RD research project, funded by European Union grants over 2018-2022. The Myology Research Centre at the Institute of Myology (team led by Gisèle Bonne) and the ERN-Euro-NMD healthcare network are also contributing to this project.

In June 2021, the European Journal of Human Genetics published a series of articles highlighting the unique characteristics of this project focusing on rare genetic diseases with an unknown molecular cause. Solve-RD contributors utilise two approaches to determine this cause:

  • conduct new regular, mass analyses of whole genome or exome sequencing data that have, until now, been inconclusive,
  • use combined multi-omics methods (RNA, proteomic, epigenomic, metabolomic sequencing, etc.).


Tangible progress in the fight against delayed diagnosis

Over the first three years of Solve-RD, an initial re-analysis of the sequencing data from 8,393 patients or families already led to the genetic diagnosis of more than 200 cases of rare diseases. These included 616 families or index cases with unresolved neuromuscular disorders, for whom the European project enabled a molecular diagnosis to be made in 22 cases, identification of candidate variants still under evaluation in 13 cases, and potential heterozygous candidate variants for recessive autosomal transmission disorders in 21 cases.

An article in the same journal thus reports the case of a patient with cerebellar hypoplasia and spinal muscular atrophy type 1 (PCH1) with congenital bone fractures. Exome sequencing proved unsuccessful. A new analysis, conducted in the context of Solve-RD, identified a homozygous variant in the TRIP4 gene.


Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases. Zurek B, Ellwanger K, Vissers LELM, et al. Eur J Hum Genet. 2021 Jun 1.


Solving patients with rare diseases through programmatic reanalysis of genome-phenome data. Matalonga L, Hernandez-Ferrer C, Piscia D et al. Eur J Hum Genet. 2021 Jun 1.


Exome reanalysis and proteomic profiling identified TRIP4 as a novel cause of cerebellar hypoplasia and spinal muscular atrophy (PCH1). Töpf A, Pyle A, Griffin H et al. Eur J Hum Genet. 2021 Jun 1.