Seraphim CE, Canton APM, Montenegro L, et al. - In the present study, the researchers described the clinical and hormonal features of a large cohort of patients with central precocious puberty (CPP) due to makorin RING finger protein 3 (MKRN3) mutations and compared the features of different types of genetic defects. The sample consisted of 716 patients with familial or idiopathic CPP screened for MKRN3 mutations and a group of 156 Brazilian girls with idiopathic CPP (ICPP) was used as a control group. Seventy-one individuals (45 girls and 26 boys from 36 families) had 18 different loss-of-function MKRN3 mutations. Computational protein modeling showed that 60% of the missense mutations were predicted to cause protein destabilization. Clinically indistinct from ICPP is the inherited premature activation of the reproductive axis triggered by loss-of-function mutations of MKRN3. The type of genetic defect, however, can influence bone age maturation and gonadotropin levels.