CUL3 and hypertensive disorder: Regarding the phenotype, in agreement with previous reports and most subjects with mutations in CUL3, these patients in the study were diagnosed with evident hyperkalemic metabolic acidosis, growth impairment, and hypertension before age of 18 years, a more severe phenotype than those with mutations in KLHL3, WNK1, or WNK4. However, contrary to the finding that the majority of CUL3 mutations in PHAII patients were de novo, this novel mutation c.1221A > G was transmitted as an autosomal dominant mode of inheritance in this family, a suggestion of no impairment of reproductive fitness.