These observations have major implications for interpreting RNA-Seq results in RTT and potentially other neurodevelopmental disorders, or in diseases of other tissues caused by mutations in genes that modulate transcription like MECP2. The existence of transcriptional buffering mechanisms in mammals raises a cautionary note for interpreting RNA-Seq steady-state results in the general context of transcriptional regulation. The gene discussed is MECP2; the disease is neurodevelopmental disorder.