Two Frameshift Mutations in MKRN3 in Turkish Patients with Familial Central Precocious Puberty

ŞİMŞEK E., Demiral M., Ceylaner S., KIREL B.

HORMONE RESEARCH IN PAEDIATRICS, cilt.87, sa.6, ss.405-411, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 87 Sayı: 6
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1159/000450923
  • Dergi Adı: HORMONE RESEARCH IN PAEDIATRICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.405-411
  • Anahtar Kelimeler: Familial central precocious puberty, MKRN3, Turkish children, IMPRINTED GENE, MISSENSE MUTATION, HYPOGONADOTROPIC HYPOGONADISM, BROTHER, DECLINE, GIRL
  • Eskişehir Osmangazi Üniversitesi Adresli: Evet

Özet

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 dem-onstrated to be involved in the pathogenesis of familial iCPP. Aim: 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 pro-bands 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. (C) 2016 S. Karger AG, Basel