Investigation of MKRN3 Mutation in Patients with Familial Central Precocious Puberty
Zehra Aycan1, Şenay Savaş-Erdeve1, Semra Çetinkaya1, Erdal Kurnaz1, Melikşah Keskin1, Nursel Muratoğlu Şahin1, Elvan Bayramoğlu1, Gülay Ceylaner21University of Health Sciences, Dr. Sami Ulus Obstetrics and Gynecology, Children’s Health and Disease Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey2İntergen Genetic Diagnosis Center, Unit of Genetics, Ankara, Turkey
Objective: There have been recent advances in the understanding of the etiology of idiopathic central precocious puberty (iCPP) including new genetic associations. The aim of this clinical study was to determine the frequency of MKRN3 mutation in cases of familial iCPP.
Methods: Potential sequence variations in the maternally imprinted MKRN3 gene were evaluated in 19 participants from 10 families using next-generation sequencing analysis.
Results: MKRN3 variation was found in only one of the 19 (5.3%) subjects. The male patient, who had a medical history of precocious puberty, had a heterozygous mutation, NM_005664.3: c.630_650delins GCTGGGC (p.P211Lfs*16). The father of this patient also had a history of precocious puberty and had the same mutation. p.P211Lfs*16 is a novel variant and it was identified as probably pathogenic by in silico analysis, consistent with the clinical findings.
Conclusion: Given that MKRN3 mutation was detected in only one patient, with a paternal history of precocious puberty, this reinforces the importance of accurate family history taking. The detected incidence of MKRN3 variants in our case series was much lower than reported elsewhere which suggests a need for further studies in Turkish iCPP patients.
Manuscript Language: English
