TY - JOUR T1 - MKRN3 levels in girls with central precocious puberty and correlation with sexual hormone levels: a pilot study. JF - Endocrine Y1 - 2018 A1 - Grandone, Anna A1 - Cirillo, Grazia A1 - Sasso, Marcella A1 - Capristo, Carlo A1 - Tornese, Gianluca A1 - Marzuillo, Pierluigi A1 - Luongo, Caterina A1 - Rosaria Umano, Giuseppina A1 - Festa, Adalgisa A1 - Coppola, Ruggero A1 - Miraglia Del Giudice, Emanuele A1 - Perrone, Laura KW - Adolescent KW - Adolescent Nutritional Physiological Phenomena KW - Anti-Mullerian Hormone KW - Case-Control Studies KW - Child KW - Child Nutritional Physiological Phenomena KW - Child, Preschool KW - Cross-Sectional Studies KW - Female KW - Follicle Stimulating Hormone KW - Gonadotropin-Releasing Hormone KW - Humans KW - Luteinizing Hormone KW - Pilot Projects KW - Puberty, Precocious KW - Ribonucleoproteins KW - Sexual Maturation AB -

PURPOSE: Recently, mutations of makorin RING-finger protein 3 (MKRN3) have been described in familial central precocious puberty. Serum levels of this protein decline before the pubertal onset in healthy girls and boys. The aim of the study is to investigate MKRN3 circulating levels in patients with central precocious puberty.

METHODS: We performed an observational cross-sectional study. We enrolled 17 patients with central precocious puberty aged 7 years (range: 2-8 years) and breast development onset <8 years; 17 prepubertal control age-matched patients aged 6.3 years (2-8.2); and 10 pubertal stage-matched control patients aged 11.4 years (9-14). Serum values of MKRN3, gonadotropins, (17)estradiol and Anti-Müllerian Hormone were evaluated and the MKRN3 genotyped in central precocious puberty patients.

RESULTS: No MKRN3 mutation was found among central precocious puberty patients. MKRN3 levels were lower in patients with central precocious puberty compared to prepubertal age-matched ones (p: 0.0004) and comparable to those matched for pubertal stage. MKRN3 levels were inversely correlated to Body Mass Index Standard Deviations (r:-0.35; p:0.02), Luteinizing Hormone (r:-0.35; p:0.03), FSH (r:-0.37; p:0.02), and (17)estradiol (r: -0.36; p:0.02).

CONCLUSIONS: We showed that girls with central precocious puberty had lower peripheral levels of MKRN3 compared to age-matched pairs and that they negatively correlated to gonadotropins, estrogen, and BMI. Our findings support the MKRN3 involvement in central precocious puberty also in absence of deleterious mutations, although our sample size is small. In addition our data suggest the role of MKRN3 in the complex mechanism controlling puberty onset and its interaction with other factors affecting puberty such as nutrition.

VL - 59 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28299573?dopt=Abstract ER - TY - JOUR T1 - MKRN3 Levels in Girls with Central Precocious Puberty during GnRHa Treatment: A Longitudinal Study. JF - Horm Res Paediatr Y1 - 2018 A1 - Grandone, Anna A1 - Cirillo, Grazia A1 - Sasso, Marcella A1 - Tornese, Gianluca A1 - Luongo, Caterina A1 - Festa, Adalgisa A1 - Marzuillo, Pierluigi A1 - Miraglia Del Giudice, Emanuele KW - Brain Diseases KW - Case-Control Studies KW - Child KW - Child, Preschool KW - Female KW - Follicle Stimulating Hormone KW - Genotype KW - Gonadotropin-Releasing Hormone KW - Humans KW - Longitudinal Studies KW - Luteinizing Hormone KW - Male KW - Puberty, Precocious KW - Ribonucleoproteins AB -

BACKGROUND: Recently, mutations of makorin RING finger protein 3 (MKRN3) have been identified in familial central precocious puberty (CPP). Serum levels of this protein decline before the pubertal onset in healthy girls and boys and are lower in patients with CPP compared to prepubertal matched pairs. The aim of our study was to investigate longitudinal changes in circulating MKRN3 levels in patients with CPP before and during GnRH analogs (GnRHa) treatment.

METHODS: We performed a longitudinal prospective study. We enrolled 15 patients with CPP aged 7.2 years (range: 2-8) with age at breast development onset < 8 years and 12 control girls matched for the time from puberty onset (mean age 11.8 ± 1.2 years). Serum values of MKRN3, gonadotropins, and 17β-estradiol were evaluated before and during treatment with GnRHa (at 6 and 12 months). The MKRN3 gene was genotyped in CPP patients. In the girls from the control group, only basal levels were analyzed.

RESULTS: No MKRN3 mutations were found among CPP patients. MKRN3 levels declined significantly from baseline to 6 months of GnRHa treatment (p = 0.0007) and from 6 to 12 months of treatment (p = 0.003); MKRN3 levels at 6 months were significantly lower than in the control girls (p < 0.0001).

CONCLUSIONS: We showed that girls with CPP had a decline in peripheral levels of MKRN3 during GnRHa treatment. Our data suggest a suppression of MKRN3 by continuous pharmacological administration of GnRHa.

VL - 90 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/30269125?dopt=Abstract ER - TY - JOUR T1 - A case of Rubinstein-Taybi syndrome associated with growth hormone deficiency in childhood. JF - Clin Endocrinol (Oxf) Y1 - 2015 A1 - Tornese, Gianluca A1 - Marzuillo, Pierluigi A1 - Pellegrin, Maria Chiara A1 - Germani, Claudio A1 - Faleschini, Elena A1 - Zennaro, Floriana A1 - Grandone, Anna A1 - Miraglia Del Giudice, Emanuele A1 - Perrone, Laura A1 - Ventura, Alessandro VL - 83 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25683362?dopt=Abstract ER -