Outcome of over 1500 matches through the Matchmaker Exchange for rare disease gene discovery: The 2-year experience of Care4Rare Canada

Genet Med. 2022 Jan;24(1):100-108. doi: 10.1016/j.gim.2021.08.014. Epub 2021 Nov 30.

Abstract

Purpose: Matchmaking has emerged as a useful strategy for building evidence toward causality of novel disease genes in patients with undiagnosed rare diseases. The Matchmaker Exchange (MME) is a collaborative initiative that facilitates international data sharing for matchmaking purposes; however, data on user experience is limited.

Methods: Patients enrolled as part of the Finding of Rare Disease Genes in Canada (FORGE) and Care4Rare Canada research programs had their exome sequencing data reanalyzed by a multidisciplinary research team over a 2-year period. Compelling variants in genes not previously associated with a human phenotype were submitted through the MME node PhenomeCentral, and outcomes were collected.

Results: In this study, 194 novel candidate genes were submitted to the MME, resulting in 1514 matches, and 15% of the genes submitted resulted in collaborations. Most submissions resulted in at least 1 match, and most matches were with GeneMatcher (82%), where additional email exchange was required to evaluate the match because of the lack of phenotypic or inheritance information.

Conclusion: Matchmaking through the MME is an effective way to investigate novel candidate genes; however, it is a labor-intensive process. Engagement from the community to contribute phenotypic, genotypic, and inheritance data will ensure that matchmaking continues to be a useful approach in the future.

Keywords: Data sharing; GeneMatcher; Matchmaker exchange; PhenomeCentral; Rare diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Canada
  • Databases, Genetic*
  • Genetic Association Studies
  • Humans
  • Information Dissemination* / methods
  • Phenotype
  • Rare Diseases* / diagnosis
  • Rare Diseases* / genetics