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Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by <i>MeCP2 mutations</i>. Nonetheless, the pathophysiological roles of <i>MeCP2 mutations</i> in the etiology of intrinsic cardiac abnormality and sudden death remain unclear. In this study, we performed a detailed functional studies (calcium and electrophysiological analysis) and RNA-sequencing-based transcriptome analysis of a pair of isogenic RTT female patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) that expressed either <i>MeCP2^wildtype</i> or <i>MeCP2^mutant</i> allele and iPSC-CMs from a non-affected female control. The observations were further confirmed by additional experiments, including Wnt signaling inhibitor treatment, siRNA-based gene silencing, and ion channel blockade. Compared with <i>MeCP2^wildtype</i> and control iPSC-CMs, <i>MeCP2^mutant</i> iPSC-CMs exhibited prolonged action potential and increased frequency of spontaneous early after polarization. RNA sequencing analysis revealed up-regulation of various Wnt family genes in <i>MeCP2^mutant</i> iPSC-CMs. Treatment of <i>MeCP2^mutant</i> iPSC-CMs with a Wnt inhibitor XAV939 significantly decreased the β-catenin protein level and <i>CACN1AC</i> expression and ameliorated their abnormal electrophysiological properties. In summary, our data provide novel insight into the contribution of activation of the Wnt/β-catenin signaling cascade to the cardiac abnormalities associated with <i>MeCP2</i> mutations in RTT.