title: Time Course of Central Precocious Puberty Development Caused by an MKRN3 Gene Mutation: A Prismatic Case.
abstract: BACKGROUND
  Loss-of-function mutations in the imprinted gene MKRN3 represent the most common known genetic defects associated with central precocious puberty (CPP).
  
  
  METHODS
  We report the first case of a girl carrying an MKRN3 mutation detected in childhood and followed until the development of pubertal signs.
  
  
  RESULTS
  The girl was screened at the age of 4 years because of a positive family history; her sister had developed CPP at 6 years of age and was found to harbor the MKRN3 p.Pro161Argfs*16 mutation, inherited from their asymptomatic father. During close follow-up, she initially developed increased growth velocity at 6 years (9 cm/year), followed by a slightly increased basal luteinizing hormone level (0.4 mIU/ml) and, ultimately, clinical thelarche with rapid progression (Tanner stage 1-3) between 6.3 and 6.7 years. In the context of a loss-of-function MKRN3 mutation and a positive family history, these features established the diagnosis of CPP and supported the initiation of treatment with a gonadotropin-releasing hormone analog. The absence of significant bone age advancement, pubic or axillary hair, or behavioral or social problems could be ascribed to the early diagnosis.
  
  
  CONCLUSIONS
  The identification of carriers of MKRN3 mutations may contribute to early diagnosis of CPP, facilitating treatment decisions and guiding genetic counseling and prompt intervention in familial cases.
authors.affiliation: Departments of Pediatrics and Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Monica F
authors.initials: MF
authors.lastname: Stecchini
authors.forename: Delanie B
authors.initials: DB
authors.lastname: Macedo
authors.forename: Ana Claudia S
authors.initials: AC
authors.lastname: Reis
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Abreu
authors.forename: Ayrton C
authors.initials: AC
authors.lastname: Moreira
authors.forename: Margaret
authors.initials: M
authors.lastname: Castro
authors.forename: Ursula B
authors.initials: UB
authors.lastname: Kaiser
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
authors.forename: Sonir R
authors.initials: SR
authors.lastname: Antonini
mesh_terms: D019943:Amino Acid Substitution; D002675:Child, Preschool; D005260:Female; D006801:Humans; D020125:Mutation, Missense; D011629:Puberty, Precocious / Q000235:genetics* / Q000503:physiopathology*; D012261:Ribonucleoproteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D012261:Ribonucleoproteins; C119425:MKRN3 protein, human; D044767:Ubiquitin-Protein Ligases