Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome

Patients with 22q11.2 deletion syndrome have heterogeneous clinical presentations including immunodeficiency, cardiac anomalies, and hypocalcemia. The syndrome arises from hemizygous deletions of up to 3 Mb on chromosome 22q11.2, a region that contains 60 genes and 4 microRNAs. MicroRNAs are important post-transcriptional regulators of gene expression, with mutations in several microRNAs causal to specific human diseases. We characterized the microRNA expression patterns in the peripheral blood of patients with 22q11.2 deletion syndrome (n = 31) compared to normal controls (n = 22). Eighteen microRNAs had a statistically significant differential expression (p < 0.05), with miR-185 expressed at 0.4 × normal levels. The 22q11.2 deletion syndrome cohort exhibited microRNA expression hyper-variability and group dysregulation. Selected microRNAs distinguished patients with cardiac anomalies, hypocalcemia, and/or low circulating T cell counts. In summary, microRNA profiling of chromosome 22q11.2 deletion syndrome/DiGeorge patients revealed a signature microRNA expression pattern distinct from normal controls with clinical relevance.

► 22q11.2 deletion syndrome patients are miR-185 haploinsufficient.
► 22q11.2/DiGeorge syndrome causes a microRNA dysregulation.
► MicroRNA profiling can identify and distinguish patients with DiGeorge syndrome.