Fibroblast Transcriptomics in Molecular Diagnostics of a Comprehensive Dystonia Cohort.

RNA-seq on skin biopsies to identify expression and splicing aberrations in dystonia-associated genes unsolved by WGS/WES

167 patients with dystonia were analyzed by RNA-seq on skin fibroblasts. More than 80% of dystonia-associated genes are detectable by this approach. Among 131 patients without a diagnosis after genomic sequencing, transcriptomic analysis identified relevant expression or splicing aberrations. The method is particularly effective at validating pathogenic effects of loss-of-function variants, with disease-relevant RNA underexpression detected in 66.7% of cases (10/15).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Dystonia is an emblematic indication for diagnostic RNA-seq: the diagnostic odyssey rate remains high despite WES/WGS, and skin fibroblasts express most implicated genes. This study aligns with the broader movement toward integrating multi-omics as second-tier diagnostics — with skin biopsy transcriptomics as a practical and accessible tool.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 2/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 8/10