While only 5 females [14, 15, 17] and 2 males [13, 15] were reported to harbor ESR1 germline mutations, all these mutations were homozygous and associated with multicystic ovaries and delayed pubertal mammary gland development in females; furthermore, the ESR1-mutated women presented with complete estrogen insensitivity, and elevated levels of serum estrogen, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) [14, 15, 17]. The gene discussed is ESR1; the disease is polycystic ovary syndrome.