Our DGE results show that DLX6-AS1, TMEM132C, FOXG1, C14orf23 and KLHDC8A are consistently among the top 10 upregulated genes at both TD11 and TD31 (Table S2A). Among these genes, FOXG1, which is one of the top 100 hubs in the magenta module, with an 8.5- and 13-fold increase in expression at TD11 and TD31, respectively (Table S2A), is a transcription factor important for the development of the telencephalon (Hanashima et al., 2004; Martynoga et al., 2005; Xuan et al., 1995). Notably, loss-of-function mutations in FOXG1 have been found in patients with atypical Rett Syndrome (Ariani et al., 2008; Bahi-Buisson et al., 2010; Shoichet et al., 2005) and confer a small brain size (Kortum et al., 2011). As the probands under investigation have large brain size, it is possible that FOXG1 may be, at least in part, involved in the modulation of the brain size phenotype, and possibly in the social disability component of the phenotype.
