title: Two Frameshift Mutations in MKRN3 in Turkish Patients with Familial Central Precocious Puberty.
abstract: BACKGROUND
  Little is known about the genetic causes responsible for idiopathic central precocious puberty (iCPP). More recently, described loss-of-function mutations in the makorin ring finger protein 3 (MKRN3) gene have been demonstrated to be involved in the pathogenesis of familial iCPP.
  
  
  OBJECTIVE
  The objective of this study was to investigate the potential role of MKRN3 in patients with familial iCPP.
  
  
  METHODS
  We investigated potential sequence variations in the maternal imprinted MKRN3 gene using Next Generation Sequencing (NGS) analysis in 31 participants from 2 families (6 participants were diagnosed with familial iCPP on the basis of clinical and hormonal findings). Six patients diagnosed with familial iCPP and their unaffected first- and second-degree relatives, including their grandparents, were screened for MKRN3 gene variants.
  
  
  RESULTS
  Two heterozygous frameshift mutations (c.441_441delG, p.H148Tfs*23 and c803_803delAT, p.M268Vfs*23) were described in the MKRN3 gene in 2 probands with familial iCPP and in some of their family members. These frameshift mutations create a premature stop codon and result in a truncated protein.
  
  
  CONCLUSIONS
  Our report further expands the MKRN3 gene mutation spectrum in patients with familial iCPP. Screening for potential MKRN3 variants should be performed in patients with familial iCPP as well as in patients with sporadic iCPP.
authors: Department of Paediatric Endocrinology, Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey.
authors: Enver
authors: E
authors: Simsek
authors: Meliha
authors: M
authors: Demiral
authors: Serdar
authors: S
authors: Ceylaner
authors: Birgul
authors: B
authors: Kırel
mesh_terms: D002648:Child; D002675:Child, Preschool; D018388:Codon, Terminator; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D011629:Puberty, Precocious / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D014421:Turkey; D044767:Ubiquitin-Protein Ligases
chemical_list: D018388:Codon, Terminator; D012261:Ribonucleoproteins; C119425:MKRN3 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: <italic>MKRN3</italic>; Familial central precocious puberty; Turkish children