ArticleNeuroendocrinology2018
Central Precocious Puberty Caused by a Heterozygous Deletion in the MKRN3 Promoter Region.
Article in Neuroendocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- High-throughput transcriptome analysis reveals a developmental increase in Acvr1c which mediates epigenetic repression of the gene encoding the pubertal brake, Makorin ring finger protein 3.NAR molecular medicine · 2025Article
- Genetics and Epigenetics of Human Pubertal Timing: The Contribution of Genes Associated With Central Precocious Puberty.Journal of the Endocrine Society · 2025Review
- Mouse Testicular Mkrn3 Expression Is Primarily Interstitial, Increases Peripubertally, and Is Responsive to LH/hCG.Endocrinology · 2023Article
- Effect of CPP-related genes on GnRH secretion and Notch signaling pathway during puberty.Biomedical journal · 2023Review
- Genetic causes of central precocious puberty.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2022Review
- Methylation status of hypothalamicFrontiers in endocrinology · 2022Article
- MKRN3 role in regulating pubertal onset: the state of art of functional studies.Frontiers in endocrinology · 2022Review
- Conservation of Imprinting and Methylation ofAnimals : an open access journal from MDPI · 2021Article
- [Clinical and molecular genetic features of 3 family cases of the central precocious puberty, due toProblemy endokrinologii · 2021Article
- Genotype-Phenotype Correlations in Central Precocious Puberty Caused by MKRN3 Mutations.The Journal of clinical endocrinology and metabolism · 2021Article
- Pathogenic and Low-Frequency Variants in Children With Central Precocious Puberty.Frontiers in endocrinology · 2021Article
- Makorin RING finger protein 3 and central precocious puberty.Current opinion in endocrine and metabolic research · 2020Article
- GENETICS IN ENDOCRINOLOGY: Genetic etiologies of central precocious puberty and the role of imprinted genes.European journal of endocrinology · 2020Review
- Heterozygous Deletions in MKRN3 Cause Central Precocious Puberty Without Prader-Willi Syndrome.The Journal of clinical endocrinology and metabolism · 2020Observational
- Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3.PLoS biology · 2019Article
- Pioneering studies on monogenic central precocious puberty.Archives of endocrinology and metabolism · 2019Review
- Article
- Central Precocious Puberty Caused by Novel Mutations in the Promoter and 5'-UTR Region of the ImprintedFrontiers in endocrinology · 2019Article
- Complex genetics of female fertility.NPJ genomic medicine · 2018Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
contextLoss-of-function mutations in the coding region of MKRN3, a maternally imprinted gene at chromosome 15q11.2, are a common cause of familial central precocious puberty (CPP). Whether MKRN3 alterations in regulatory regions can cause CPP has not been explored to date. We aimed to investigate potential pathogenic variants in the promoter region of MKRN3 in patients with idiopathic CPP. PATIENTS/
methodsA cohort of 110 patients with idiopathic CPP was studied. Family history of precocious sexual development was present in 25%. Mutations in the coding region of MKRN3 were excluded in all patients. Genomic DNA was extracted from peripheral blood leukocytes, and 1,100 nucleotides (nt) of the 5'-regulatory region of MKRN3 were amplified and sequenced. Luciferase assays were performed in GT1-7 cells transiently transfected with plasmids containing mutated and wild-type MKRN3 promoter.
resultsWe identified a rare heterozygous 4-nt deletion (c.-150_-147delTCAG; -38 to -41 nt upstream to the transcription start site) in the proximal promoter region of MKRN3 in a girl with CPP. In silico analysis predicted that this deletion would lead to the loss of a binding site for a downstream res-ponsive element antagonist modulator (DREAM), a potential transcription factor for MKRN3 and GNRH1 expression. Luciferase assays demonstrated a significant reduction of MKRN3 promoter activity in transfected cells with a c.-150_- 147delTCAG construct plasmid in both homozygous and heterozygous states when compared with cells transfected with the corresponding wild-type MKRN3 promoter region.
conclusionA rare genetic alteration in the regulatory region of MKRN3 causes CPP.
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