Evidence map›Paper›PMID 39324648›Full record

ArticleThe Journal of clinical endocrinology and metabolism2025

Comprehensive Study on Central Precocious Puberty: Molecular and Clinical Analyses in 90 Patients.

Hiromune Narusawa, Tomoe Ogawa, Hideaki Yagasaki, Keisuke Nagasaki, Tatsuki Urakawa, Tomohiro Saito, Shun Soneda, Saori Kinjo, Shinichiro Sano, Mitsukazu Mamada and 8 more

Abstract read
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In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Genetic and Epigenetic Contributions to Central Precocious Puberty.The Journal of clinical endocrinology and metabolism · 2025
    Article
  5. Diagnostics (Basel, Switzerland) · 2025
    Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Hiromune NarusawaDepartment of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
Tomoe OgawaDepartment of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
Hideaki YagasakiDepartment of Pediatrics, Faculty of Medicine, University of Yamanashi, Chuo 409-3898, Japan.
Keisuke NagasakiDivision of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Science, Niigata 951-8510, Japan.ORCID 0000-0002-5882-661X
Tatsuki UrakawaDepartment of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
Tomohiro SaitoDepartment of Pediatrics, Yamanashi Prefectural Central Hospital, Kofu 400-0027, Japan.
Shun SonedaTanaka Growth Clinic, Tokyo 158-0097, Japan.
Saori KinjoDepartment of Pediatrics, Okinawa Chubu Hospital, Uruma 904-2293, Japan.
Shinichiro SanoDepartment of Pediatric Endocrinology and Metabolism, Shizuoka Children's Hospital, Shizuoka 420-0953, Japan.
Mitsukazu MamadaDepartment of Pediatrics, Japanese Red Cross Wakayama Medical Center, Wakayama 640-8558, Japan.
Shintaro TerashitaDepartment of Pediatrics, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan.
Sumito DatekiDepartment of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
Satoshi NarumiDepartment of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
Yasuhiro NaikiDivision of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo 157-8535, Japan.
Reiko HorikawaDivision of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo 157-8535, Japan.ORCID 0000-0003-3429-3246
Tsutomu OgataDepartment of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.ORCID 0000-0001-7178-9991
Maki FukamiDepartment of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.ORCID 0000-0001-9971-4035
Masayo KagamiDepartment of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.ORCID 0000-0003-3020-455X

Funding

Japan Agency for Medical Research and Development 20ek0109373h0003Japan Society for the Promotion of Science JP20K08178National Center for Child Health and Development 2019B-4Novo Nordisk Pharma LtdTakeda Science FoundationThe Foundation for Growth ScienceThe Japanese Society for Pediatric Endocrinology Future Development
6 · The paper itself

Abstract

contextDefects in MKRN3, DLK1, KISS1, and KISS1R and some disorders, such as Temple syndrome (TS14), cause central precocious puberty (CPP). Recently, pathogenic variants (PVs) in MECP2 have been reported to be associated with CPP.

objectiveWe aimed to clarify the contribution of (epi)genetic abnormalities to CPP and clinical and hormonal features in each etiology.

methodsWe conducted targeted sequencing for MKRN3, DLK1, MECP2, KISS1, and KISS1R and methylation analysis for screening of imprinting disorders such as TS14 associated with CPP in 90 patients with CPP (no history of brain injuries and negative brain magnetic resonance imaging) and collected their clinical and laboratory data. We measured serum DLK1 levels in 3 patients with TS14 and serum MKRN3 levels in 2 patients with MKRN3 genetic defects, together with some etiology-unknown patients with CPP and controls.

resultsWe detected 8 patients with TS14 (6, epimutation; 1, mosaic maternal uniparental disomy chromosome 14; 1, microdeletion) and 3 patients with MKRN3 genetic defects (1, PV; 1, 13-bp deletion in the 5'-untranslated region [5'-UTR]; 1, microdeletion) with family histories of paternal early puberty. There were no patients with PVs identified in MECP2, KISS1, or KISS1R. We confirmed low serum MKRN3 level in the patient with a deletion in 5'-UTR. The median height at initial evaluation of TS14 patients was lower than that of all patients. Six patients with TS14 were born small for gestational age (SGA).

conclusion(Epi)genetic causes were identified in 12.2% of patients with CPP at our center. For patients with CPP born SGA or together with family histories of paternal early puberty, (epi)genetic testing for TS14 and MKRN3 genetic defects should be considered.

Indexed as

Puberty, PrecociousCalcium-Binding ProteinsChildChild, PreschoolFemaleHumansInfantIntercellular Signaling Peptides and ProteinsKisspeptinsMaleMembrane ProteinsMethyl-CpG-Binding Protein 2MutationReceptors, Kisspeptin-1Ubiquitin-Protein LigasesCalcium-Binding ProteinsDLK1 protein, humanIntercellular Signaling Peptides and ProteinsKISS1 protein, humanKISS1R protein, humanKisspeptinsMECP2 protein, humanMembrane ProteinsMethyl-CpG-Binding Protein 2MKRN3 protein, humanReceptors, Kisspeptin-1Ubiquitin-Protein Ligasescentral precocious pubertyimprinted genesimprinting disordersMECP2MKRN3temple syndrome

Identifiers

PMID39324648

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.