Proteomics identify disease-associated variants in patients with rare diseases undiagnosed after genome sequencing.

Proteomics identified disease-associated variants in 64% of undiagnosed rare disease patients after genome sequencing, enhancing diagnostic success.

• Why it matters: Most patients with rare diseases remain without a genetic diagnosis despite genome sequencing, limiting understanding and treatment options.
• What they did: Serum proteomic profiling of 424 patients using the Olink Explore 1536 assay revealed lower protein outliers that confirmed or suggested genetic diagnoses, including candidate gene-disease links.
• The result: This approach improved diagnosis and gene discovery, demonstrating proteomics' potential to complement genome sequencing, though its effectiveness depends on tissue-specific protein expression and platform sensitivity.