Convergent Transcriptomic Signatures in Blood Link Lumbar Disc Herniation and Cervical Artery Dissection in Young Adults

Recurrent lumbar disc herniation (rLDH) and cervical artery dissection (CeAD) are significant neurological manifestations of undifferentiated connective tissue dysplasia (UCTD) in young adults. Molecular and histopathological evidence points to impaired cellular differentiation and aberrant extracellular matrix organization in these patients. Nevertheless, the pathogenic mechanisms of UCTD and the basis for its clinical heterogeneity remain largely unknown. Here, we conducted the first comparative transcriptome-wide analysis of peripheral blood mRNA in two UCTD cohorts—19 patients with CeAD and 12 with rLDH—alongside 18 healthy volunteers. Both UCTD cohorts exhibited common transcriptomic signatures indicating suppressed translation and RNA processing, mitochondrial dysfunction, and premature cellular senescence. Notably, the activated compensatory pathways, functionally annotated to small GTPase signaling, diverged between the cohorts. The rLDH group displayed a transcriptional signature of generalized extracellular matrix reorganization, whereas the CeAD cohort showed alterations primarily involved in cellular differentiation, adhesion, migration, and intercellular communication. Further differential analysis of upstream regulatory genes and splicing variants, complemented by single-cell RNA sequencing of tissue biopsies, is warranted to elucidate the precise mechanisms that drive the clinical heterogeneity of UCTD within the context of a potential sporadic ribosomopathy.