Publication: Molecular analysis of MKRN3 gene in Turkish girls with sporadic and familial idiopathic central
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Date
2023-03-01
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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.
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Tıp, Dahili Tıp Bilimleri, Çocuk Sağlığı ve Hastalıkları, İç Hastalıkları, Endokrinoloji ve Metabolizma Hastalıkları, Sağlık Bilimleri, Medicine, Internal Medicine Sciences, Child Health and Diseases, Internal Diseases, Endocrinology and Metabolic Diseases, Health Sciences, ENDOKRİNOLOJİ VE METABOLİZMA, Klinik Tıp, Klinik Tıp (MED), PEDİATRİ, ENDOCRINOLOGY & METABOLISM, CLINICAL MEDICINE, Clinical Medicine (MED), PEDIATRICS, Pediatri, Endokrin ve Otonom Sistemler, Pediatri, Perinatoloji ve Çocuk Sağlığı, Endokrinoloji, Diyabet ve Metabolizma, Endokrinoloji, Yaşam Bilimleri, Pediatrics, Endocrine and Autonomic Systems, Pediatrics, Perinatology and Child Health, Endocrinology, Diabetes and Metabolism, Endocrinology, Life Sciences, central precocious puberty, familial, makorin, MKRN3 mutation, pubertal onset, CENTRAL PRECOCIOUS PUBERTY, IMPRINTED GENE, PRADER-WILLI, MKRN3 MUTATIONS, VARIANTS
Citation
KIRKGÖZ 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, 2023