In addition, both loss-of-function mutations of ring finger protein 135 (RNF135) and microdeletion of NF1-REPa to REPb including RNF135 contribute to an overgrowth syndrome including tall stature, macrocephaly, dysmorphic features, and variable additional features in NF1 patients (38). Here, RNF135 is linked to overgrowth syndrome.