We identified that methylating enzymes like METTL16, WTAP, CBLL1, RBM15B, and ZC3H13 were scarcely expressed and the demethylating enzyme ALKBH5, along with reading protein-related genes, such as, IGF2BP2 and YTHDF3, were highly expressed in T versus N. In addition, we detected differential regulation of other m6A-methylated RNAs like RBM15, YTHDF3, IGF2BP1, IGF2BP3, and multiple mRNAS, micRNA, and LNC RNA, which were hypo-methylated in T versus N. Given these evidences, we believe that the m6A-mediated methylation is crucial for the pathogenesis of HbH-CS. This evidence concerns the gene RBM15B and Cowden syndrome 1.