Low Frequency of MKRN3 Mutations in Central Precocious Puberty Among Korean Girls.

Mutations of MKRN3, the gene encoding makorin RING-finger protein 3, lead to central precocious puberty (CPP). The aim of this study was to investigate mutations of the MKRN3 gene in Korean girls with CPP. Two hundred-sixty Korean girls with idiopathic CPP were included. Auxological and endocrine parameters were measured, and the entire MKRN3 gene was directly sequenced. MKRN3 gene analysis revealed one novel nonsense mutation (p.Gln281 *) and 6 missense variants (p.Ile100Phe, p.Gly196Val, p.Ile204Thr, p.Gln226Pro, p.Lys233Asn, and p.Ser396Arg). The novel nonsense mutation (p.Gln281 *) was a heterozygous C>T nucleotide change (c.841C>T) predicted to result in a truncated protein due to a premature stop codon in the MKRN3 gene. The nonsense mutation (p.Gln281 *) was only identified in one of the girls and her younger brother. Compared to previous reports on MKRN3 mutations in familial and sporadic cases of CPP, the present study reveals a relatively low number of MKRN 3 mutations in Korean girls with CPP. Larger samples of children with CPP and MKRN3 mutations are necessary in order to clarify whether the clinical course of puberty may differ as compared to idiopathic CPP.

The Association between Bone Age Advancement and Insulin Resistance in Prepubertal Obese Children.

OBJECTIVE: Obesity is associated with bone age (BA) advancement, but the underlying mechanisms remain unclear. The objective of this study was to investigate the association between BA maturation and insulin levels in obese children. METHODS: In this cross-sectional study of 93 prepubertal obese children, anthropometric data and hormonal values were measured. Subjects were divided into 2 groups based on the difference between BA and chronological age (CA) (noted as BA-CA). RESULTS: The study population included 39 (41.9%) males and 54 (58.1%) females with a mean age of 7.4±1.5 years. The advanced bone age group defined as BA-CA>1 year (n=44) had significantly higher HOMA-IR and fasting insulin levels, and lower quantitative insulin sensitivity check index (QUICKI). BA-CA was significantly correlated with fasting insulin (r=0.255, P=0.014), HOMA-IR (r=0.230, P=0.027), and QUICKI (r=- 0.301, P=0.003). Also, height SDS was significantly associated with ΔBA-CA (r=0.417, P<0.001). In the multiple regression analysis, HOMA-IR was identified as a significant independent predictor of BA-CA. CONCLUSION: Bone age is more advanced in obese children with hyperinsulinemia and insulin resistance. These findings suggest that insulin may affect skeletal maturation.