MECP2 and Rett syndrome: Over 80% of patients with RTT have mutations in exons 3 or 4 of MECP2. The identification of disease-relevant mutations in exon 1 led to the likelihood that MeCP2_E1 is the etiologically relevant protein isoform for Rett [9,13,14], later confirmed by studies of mouse knockouts specific to isoform MeCP2_e2 [15], and has also led to the inclusion of exon 1 in diagnostic sequencing for Rett syndrome.