In this study, we identified a novel synonymous mutation c.1221A > G (p.Glu407Glu) in four patients from a Chinese family, and sound evidence from in vivo and in vitro splicing assays confirmed this variant led to abnormal skipping of exon 9 as did other CUL3 mutations associated with PHAII. This evidence concerns the gene CUL3 and pseudohypoaldosteronism type 2.