Enrichment and Correlation Analysis of Serum miRNAs in Comorbidity Between Arnold-Chiari and Tourette Syndrome Contribute to Clarify Their Molecular Bases

Due to its rarity, coupled to a multifactorial and very heterogeneous nature, the molecular etiology of Arnold-Chiari (AC) syndrome remains almost totally unknown. Its relationship with other neuropsychiatric disorders such as Tourette syndrome (TS) is also undetermined. The rare comorbid status between both disorders (ACTS) complicates the framework of diagnosis and negatively affects the patients' quality of life. In this exploratory study, we aimed to identify serum microRNA expression profiles as molecular fingerprints for AC, TS, and ACTS, by using a high-throughput approach. For this aim, 10 AC patients, 11 ACTS patients, 6 TS patients, and 8 unaffected controls (NC) were recruited. Nine miRNAs resulted significantly differentially expressed (DE): let-7b-5p (upregulated in ACTS vs. TS); miR-21-5p (upregulated in ACTS vs. AC; downregulated in AC vs. TS); miR-23a-3p (upregulated in TS vs. NCs; downregulated in AC vs. TS); miR-25-3p (upregulated in AC vs. TS and NCs; downregulated in ACTS vs. AC); miR-93-5p (upregulated in AC vs. TS); miR-130a-3p (downregulated in ACTS and TS vs. NCs); miR-144-3p (downregulated in ACTS vs. AC; upregulated in AC vs. TS); miR-222-3p (upregulated in ACTS vs. NCs); miR-451a (upregulated in AC vs. TS and NCs; in ACTS vs. NCs). Altered expression of miRNAs was statistically correlated to neuroimaging and neuropsychological anomalies. Furthermore, computational analyses indicated that DE miRNAs are involved in AC and TS pathomechanisms. Finally, we propose the dysregulation of the miRNA set as a potential molecular tool for supporting the current diagnosis of AC, TS, and ACTS by using liquid biopsies, in an unbiased and non-invasive way.