ESR1 and Infertility: For the unaffected mother and sister of the proband harboring heterozygous ESR1 mutation (p.R394H), they had normal puberty and underwent menarche at 14 and 15 years of age, respectively; furthermore, the proband’s mother has given birth to seven children and thus should be fertile [15], contrary to the secondary infertility of the patient in the present study.