Molecular analysis of MKRN3 gene in Turkish girls with sporadic and familial idiopathic central precocious puberty

Tarık Kırkgöz; Sare Betül Kaygusuz; Ceren Alavanda; Didem Helvacıoğlu; Zehra Yavaş Abalı; Büşra Gürpınar Tosun; Mehmet Eltan; Tuba Seven Menevşe; Tulay Guran; Ahmet Arman; Serap Turan; Abdullah Bereket

doi:10.1515/jpem-2022-0645

Article

Molecular analysis of MKRN3 gene in Turkish girls with sporadic and familial idiopathic central precocious puberty

Tarık Kırkgöz , Sare Betül Kaygusuz , Ceren Alavanda , Didem Helvacıoğlu , Zehra Yavaş Abalı , Büşra Gürpınar Tosun , Mehmet Eltan , Tuba Seven Menevşe , Tulay Guran , Ahmet Arman , Serap Turan and Abdullah Bereket

Published/Copyright: March 9, 2023

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 36 Issue 4

Abstract

Objectives

Central precocious puberty (CPP) develops as a result of early stimulation of the hypothalamic-pituitary-gonadal (HPG) axis. The loss-of-function mutations in the Makorin-ring-finger3 (MKRN3) gene appear to be the most common molecular cause of familial CPP. We aimed to identify MKRN3 gene mutations in our CPP cohort and to investigate the frequency of MKRN3 mutations.

Methods

102 patients with CPP included. 53 of them had family history of CPP in the first and/or second-degree relatives. MKRN3 gene was analyzed by next-generation sequencing.

Results

Possible pathogenic variants were found in 2/53 patients with family history of CPP (3.8%) and 1/49 patient without family history (2%). A novel heterozygous c.1A>G (p.Met1Val) mutation, a novel heterozygous c.683_684delCA (p.Ser228*) and a previously reported c.482dupC (Ala162Glyfs*) frameshift variations were detected. The two novel variants are predicted to be pathogenic in silico analyses.

Conclusions

In our cohort, possible pathogenic variants in MKRN3 gene were detected in 2.9% of the total cohort, 3.8% of the familial and 2% of the nonfamilial cases, slightly lower than that reported in the literature. Two novel variants detected contribute to the molecular repertoire of MKRN3 defects in CPP. Classical pattern of paternal inheritance has been demonstrated in all three cases. However, the father of the patient 3 did not have history of CPP suggesting that the father inherited this variant from his mother and had phenotype skipping. Therefore, we emphasize that the absence of history of CPP in the father does not exclude the possibility of a MKRN3 mutation.

Keywords: central precocious puberty; familial; makorin; MKRN3 mutation; pubertal onset

Corresponding author: Abdullah Bereket, Professor, Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Marmara University Asaf Ataseven Hospital Aydınevler Başıbüyük Samandıra Yolu 34854 Maltepe, Istanbul, Türkiye, Phone: +90 2166061141-1524, E-mail: abdullahbereket@gmail.com

Acknowledgments

We would like to thank the children and their parents who participated in this study.

Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: This study was approved by the local Ethics Committee in light of the Helsinki Declaration (09.2020.1325).

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Received: 2022-12-29

Accepted: 2023-02-20

Published Online: 2023-03-09

Published in Print: 2023-04-25

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https://doi.org/10.1515/jpem-2022-0645

Keywords for this article

central precocious puberty; familial; makorin; MKRN3 mutation; pubertal onset