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

Abstract

<b><i>Background:</i></b> 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 <i>(MKRN3)</i> gene have been demonstrated to be involved in the pathogenesis of familial iCPP. <b><i>Aim:</i></b> The objective of this study was to investigate the potential role of <i>MKRN3</i> in patients with familial iCPP. <b><i>Methods:</i></b> We investigated potential sequence variations in the maternal imprinted <i>MKRN3</i> 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 <i>MKRN3</i> gene variants. <b><i>Results:</i></b> Two heterozygous frameshift mutations (c.441_441delG, p.H148Tfs*23 and c803_803delAT, p.M268Vfs*23) were described in the <i>MKRN3 </i>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. <b><i>Conclusions:</i></b> Our report further expands the <i>MKRN3</i> gene mutation spectrum in patients with familial iCPP. Screening for potential <i>MKRN3</i> variants should be performed in patients with familial iCPP as well as in patients with sporadic iCPP.