The genetic link between mutations in the MECP2 gene encoding the methyl-CpG–binding protein and Rett syndrome (RTT), an X-linked neurodevelopmental disorder affecting approximately 1 in 10,000 girls, was first reported in this journal (Nat. Genet. 23, 185–188, 1999). Although the MeCP2-mediated epigenetic mechanism causing neurological symptoms in RTT has been well studied, little is known about the etiology of cardiorespiratory symptoms of RTT, which contribute to a high incidence of sudden unexpected death. Jeffrey Neul and colleagues report that 18.5% of individuals with RTT show prolonged QT components (long-QT) in their electrocardiograms (Sci. Transl. Med. 3, 113ra125, 2011 ). The authors examined Mecp2-null mice and observed long-QT, tachycardia and cardiac arrhythmia in young hemizygous males and older heterozygous females. Nervous system–specific ablation of Mecp2 led to the same phenotypes. Long-QT symptom results from slow repolarization of the autonomic innervation to the heart. The authors show that the cardiac phenotype of Mecp2-null mice can be rescued by a sodium channel blocker but not by a β-adrenergic receptor antagonist, suggesting delayed sodium channel closure as the disease mechanism.
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Peng, W. Cardiac symptoms of Rett syndrome. Nat Genet 44, 120 (2012). https://doi.org/10.1038/ng.1097
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DOI: https://doi.org/10.1038/ng.1097