Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in Rett syndrome

Using the largest patient cohort studied (1052 patients) with Rett syndrome (RTT), we investigated whether individual mutations give rise to the observed phenotypic variability.  We identified groups of point mutations, deletions and insertions that were particularly severe in both typical and atypical RTT, as well as groups of mutations were less severe.  Our data suggest that for most mutations types, clinical severity progresses with age.  We found that ambulation, hand use, and age of onset of stereotypies are associated with overall disease severity.  We hope these findings will be a valuable resource to the RTT community. (By Dr. Michelle Olsen, http://jmg.bmj.com/content/early/2014/01/07/jmedgenet-2013-102113 )