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Record W4403148577 · doi:10.1210/jendso/bvae163.1523

8151 The Genetic Etiology Is a Relevant Cause of Central Precocious Puberty

2024· article· en· W4403148577 on OpenAlex
Ana Pinheiro Machado Canton, Carlos Eduardo Seraphim, Luciana Ribeiro Montenegro, Ana Cristina Krepsichi, Berenice B. Mendonça, Ana Cláudia Latronico, Vinícius Nahime Brito

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueJournal of the Endocrine Society · 2024
Typearticle
Languageen
FieldMedicine
TopicGrowth Hormone and Insulin-like Growth Factors
Canadian institutionsWiLAN (Canada)
Fundersnot available
KeywordsEtiologyMedicinePediatricsInternal medicine

Abstract

fetched live from OpenAlex

Abstract Disclosure: A.P. Canton: None. C.E. Seraphim: None. L.R. Montenegro: None. A. Krepsichi: None. B.B. Mendonca: None. A. Latronico: None. V.N. Brito: None. Background: The etiology of central precocious puberty (CPP) has expanded with the identification of new genetic causes, including the monogenic deficiency of MKRN3 in familial cases. Objectives: To assess the prevalence of CPP causes and the predictors of genetic involvement in this phenotype. Methods: A single-center retrospective cohort study was performed for an etiological survey of patients with CPP. All patients had detailed medical history, deep phenotyping, and brain MRI. Patients with CPP and no pathological brain lesions, previously considered idiopathic forms, were submitted to genetic studies, mainly DNA sequencing studies, genomic microarray, and methylation analysis. Results: We assessed 270 patients (241 girls) with CPP; 50 (18.5%) patients had CPP-related brain lesions, whereas 220 (81.5%) patients had normal brain MRI. Of the latter, 174 (165 girls and 9 boys) were included for genetic studies. Genetic etiologies were identified in 22 patients (20 girls and 2 boys), indicating an overall frequency of genetic CPP of 12.6%, which was higher in boys (22.2%) than in girls (12.1%). The most common genetic defects were MKRN3, DLK1, and MECP2 loss-of-function mutations, followed by 14q32.2 imprinting defects (Temple syndrome). Univariate logistic regression identified positive family history (OR 3.3; 95%CI 1.3-8.3; p=0.01) and associated neurodevelopmental disorders (OR 4.1; 95%CI 1.3-13.5; p=0.02) as clinical predictors of genetic CPP. A novel algorithm for investigating the etiology of CPP was set up, including genetic studies guided by clinical parameters. Conclusion: Distinct genetic causes were identified in 12.6% of CPP patients previously classified as idiopathic, revealing the genetic etiology as a relevant cause of CPP in both sexes. Family history and neurodevelopmental disorders were identified as predictors of genetic CPP, recommending that both factors should be actively investigated in the CPP workup. A novel algorithm for investigating the etiology of CPP can be practice-changing for those who assist children with precocious puberty. Presentation: 6/2/2024

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.552
Threshold uncertainty score0.402

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.269
Teacher spread0.254 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it