In total, we identified 15 patients (8 female patients and 7 male patients) with central precocious puberty who carried mutations in MKRN3 that are predicted to be loss-of-function or damaging mutations. Each of these patients had clinical and hormonal features that are typical of premature activation of the reproductive axis, including early pubertal signs, such as breast development or testicular enlargement and pubic hair, advanced linear growth and bone age, and elevated basal luteinizing hormone levels, elevated GnRH-stimulated luteinizing hormone levels, or both. The median age at the onset of puberty in the girls was 5.75 years, ranging from 5.0 to 6.5 years (Table 1). In boys with mutations in MKRN3, the median age at the onset of puberty was 8.1 years, ranging from 5.9 to 8.5 years (Table 1). The precise time of onset of puberty was not clear in two boys, but clinical and laboratory assessment confirmed the diagnosis of central precocious puberty. The proband in Family A and her brother (Patients III-1 and III-2 in Fig. 1) have esotropia, which is a minor diagnostic criterion for the
