Decreased miRNA expression in Klinefelter syndrome

The widely variable phenotypic spectrum and the different symptom severity in men with Klinefelter syndrome (KS) suggest a role for epigenetic mediators. Therefore, the aim of this study was to evaluate the possible involvement of miRNAs in the clinical manifestations of KS. To accomplish this, we performed a transcriptome analysis in peripheral blood mononuclear cells (PBMCs) of 10 non-mosaic KS patients , 10 aged-matched healthy male and 10 aged-matched healthy female controls with normal karyotype. After RNA extraction from PBMC and the preparation of small RNA libraries, the samples were sequenced using next generation high-throughput sequencing technology. Expression profiling analysis revealed a significant differential expression of 2 miRNAs in KS compared to male controls. In particular, MIR3648 resulted significantly (p<0.0001) down-regulated by -19.084- fold, while MIR3687was non-expressed at all (p<0.0001) in KS patients. These results were confirmed by qRT-PCR. The functional analysis of the two transcripts showed that they seem to play a role in breast cancer, hemopoietic abnormalities, immune defects and adipocyte differentiation and fat cell maturation. Therefore, we speculate that both miRNAs may play a role in the immune and metabolic disorders and in the risk of breast cancer development in men with KS.