In this study, we identified two novel mutations of FOXL2 in two Han Chinese families with BPES type I by screening FOXL2. The aim of the present work was to comparatively evaluate the effect of the novel mutations on FOXL2 bioactivity via in vitro functional analysis and delineate the correlation between the two novel FOXL2 mutations and the types of BPES. Here, FOXL2 is linked to blepharophimosis, ptosis, and epicanthus inversus syndrome.