title: MKRN3 levels in girls with central precocious puberty and correlation with sexual hormone levels: a pilot study.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Woman, Child, General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Grandone
authors.affiliation: Department of Woman, Child, General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Cirillo
authors.affiliation: Department of Woman, Child, General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Sasso
authors.affiliation: Department of Woman, Child, General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Capristo
authors.affiliation: Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tornese
authors.affiliation: Department of Woman, Child, General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy. pierluigi.marzuillo@gmail.com.
authors.forename: Pierluigi
authors.identifier: 0000-0003-4682-0170
authors.initials: P
authors.lastname: Marzuillo
authors.affiliation: Department of Woman, Child, General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Luongo
authors.affiliation: Department of Woman, Child, General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Rosaria Umano
authors.affiliation: Department of Woman, Child, General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Adalgisa
authors.initials: A
authors.lastname: Festa
authors.affiliation: Department of Woman, Child, General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Ruggero
authors.initials: R
authors.lastname: Coppola
authors.affiliation: Department of Woman, Child, General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Miraglia Del Giudice
authors.affiliation: Department of Woman, Child, General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Perrone
mesh_terms: D000293:Adolescent; D017195:Adolescent Nutritional Physiological Phenomena; D054304:Anti-Mullerian Hormone / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002664:Child Nutritional Physiological Phenomena; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D007987:Gonadotropin-Releasing Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D010865:Pilot Projects; D011629:Puberty, Precocious / Q000097:blood / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D012741:Sexual Maturation / Q000235:genetics; D044767:Ubiquitin-Protein Ligases
chemical_list: D012261:Ribonucleoproteins; D007987:Gonadotropin-Releasing Hormone; D054304:Anti-Mullerian Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C119425:MKRN3 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Central precocious puberty; Genetics; MKRN3; Puberty