KIRKGÖZ, TARIKKAYGUSUZ, SARE BETÜLALAVANDA, CERENGÜRPINAR TOSUN, BUŞRAELTAN, MEHMETSEVEN MENEVŞE, TUBAGÜRAN, TÜLAYARMAN, AHMETDEMİRCİOĞLU, SERAPBEREKET, ABDULLAH2023-03-272023-03-272023-03-01KIRKGÖZ T., KAYGUSUZ S. B., ALAVANDA C., Helvacioglu D., Abali Z. Y., GÜRPINAR TOSUN B., ELTAN M., SEVEN MENEVŞE T., GÜRAN T., ARMAN A., et al., "Molecular analysis of MKRN3 gene in Turkish girls with sporadic and familial idiopathic central", JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM, 20230334-018Xhttps://hdl.handle.net/11424/287839Objectives: 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.enginfo:eu-repo/semantics/openAccessTıpDahili Tıp BilimleriÇocuk Sağlığı ve Hastalıklarıİç HastalıklarıEndokrinoloji ve Metabolizma HastalıklarıSağlık BilimleriMedicineInternal Medicine SciencesChild Health and DiseasesInternal DiseasesEndocrinology and Metabolic DiseasesHealth SciencesENDOKRİNOLOJİ VE METABOLİZMAKlinik TıpKlinik Tıp (MED)PEDİATRİENDOCRINOLOGY & METABOLISMCLINICAL MEDICINEClinical Medicine (MED)PEDIATRICSPediatriEndokrin ve Otonom SistemlerPediatri, Perinatoloji ve Çocuk SağlığıEndokrinoloji, Diyabet ve MetabolizmaEndokrinolojiYaşam BilimleriPediatricsEndocrine and Autonomic SystemsPediatrics, Perinatology and Child HealthEndocrinology, Diabetes and MetabolismEndocrinologyLife Sciencescentral precocious pubertyfamilialmakorinMKRN3 mutationpubertal onsetCENTRAL PRECOCIOUS PUBERTYIMPRINTED GENEPRADER-WILLIMKRN3 MUTATIONSVARIANTSarticle10.1515/jpem-2022-0645