Evidence map›Paper›PMID 41451896›Full record

ArticleObesity (Silver Spring, Md.)2026

Targeted Next-Generation Sequencing of the Leptin-Melanocortin Pathway in Severe Obesity.

Nathan Faccioli, Chrisitne Poitou, Mathieu Georget, Françoise Bertin, Ahlam Azar-Kolakez, Claire Carette, Pauline Faucher, Blandine Gatta-Cherifi, Julie Gonneau-Lejeune, Agnès Linglart and 3 more

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Article in Obesity (Silver Spring, Md.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

13 authors.

Nathan FaccioliAP-HP, Trousseau Hospital, Department of Pediatric Nutrition and Gastroenterology, Reference Center for Rare Diseases PRADORT (Prader-Willi Syndrome and Other Rare Forms of Obesity With Eating Behavior Disorders), Sorbonne University, Paris, France.ORCID 0000-0002-1230-5675
Chrisitne PoitouINSERM, Nutrition and Obesity: Systemic Approaches, NutriOmics Research Unit, Sorbonne University, Paris, France.
Mathieu GeorgetAP-HP, Pitie-Salpetriere Hospital, Functional Unit for the Genetics of Obesity and Dyslipidemia, Endocrine and Oncology Biochemistry Department, Sorbonne University, Paris, France.
Françoise BertinAP-HP, Pitie-Salpetriere Hospital, Functional Unit for the Genetics of Obesity and Dyslipidemia, Endocrine and Oncology Biochemistry Department, Sorbonne University, Paris, France.
Ahlam Azar-KolakezDepartment of Pediatric Endocrinology and Diabetology, Reference Center for Growth and Development Endocrine Diseases, University Paris Cite, AP-HP, Robert Debre University Hospital, Paris, France.
Claire CaretteAP-HP, Georges Pompidou European Hospital, Department of Nutrition, Specialized Obesity Centre & INSERM UMRS 1149, University Paris Cite, Paris, France.ORCID 0000-0002-8175-0369
Pauline FaucherINSERM, Nutrition and Obesity: Systemic Approaches, NutriOmics Research Unit, Sorbonne University, Paris, France.
Blandine Gatta-CherifiHaut Leveque Hospital, Department of Endocrinology, Diabetology, Metabolic Diseases and Nutrition, University of Bordeaux, Pessac, France.ORCID 0000-0002-7399-1330
Julie Gonneau-LejeuneFélix-Guyon Hospital, Department of Pediatrics, Saint-Denis, University of La Reunion, Reunion, France.
Agnès LinglartAP-HP, INSERM, Bicetre Paris Saclay Hospital, Endocrinology and Diabetology for Children, University Paris-Saclay, Le Kremlin-Bicetre, France.
Karine ClémentINSERM, Nutrition and Obesity: Systemic Approaches, NutriOmics Research Unit, Sorbonne University, Paris, France.
Johanne Le Beyec‐Le BihanAP-HP, Pitie-Salpetriere Hospital, Functional Unit for the Genetics of Obesity and Dyslipidemia, Endocrine and Oncology Biochemistry Department, Sorbonne University, Paris, France.
Béatrice DubernAP-HP, Trousseau Hospital, Department of Pediatric Nutrition and Gastroenterology, Reference Center for Rare Diseases PRADORT (Prader-Willi Syndrome and Other Rare Forms of Obesity With Eating Behavior Disorders), Sorbonne University, Paris, France.

Funding

French Pediatric Society (Société Française de Pédiatrie) cofounded by Novo Nordisk Laboratory 18000 €
6 · The paper itself

Abstract

objectivePathogenic variants in five established leptin-melanocortin pathway genes (LEP, LEPR, MC4R, PCSK1, POMC) are associated with severe early-onset obesity and are targets for emerging treatments. However, these variants are rare in these patients, suggesting the involvement of additional genes interacting with this pathway.

methodsNext-generation sequencing (NGS) analysis was performed in 395 patients with severe obesity, including 213 children (mean BMI: 56.3 kg/m

resultsPathogenic heterozygous variants were identified in 34 patients (8.6%), 18 of them harboring pathogenic variants in the 15 additional genes. In adults, early-onset obesity was more frequent in potentially pathogenic variants carriers than in non-carriers (83.3% vs. 55.0%, p = 0.04). No differences were observed in the other phenotypic characteristics.

conclusionsThis supports the relevance of expanded genetic testing in severe obesity. Early-onset obesity remains a key clinical feature to guide genetic investigation and identify patients who may benefit from early personalized care and targeted treatments.

Indexed as

LeptinMelanocortinsObesity, MorbidAdolescentAdultAge of OnsetChildChild, PreschoolFemaleHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedPhenotypePro-OpiomelanocortinProprotein Convertase 1LEP protein, humanLEPR protein, humanLeptinMC4R protein, humanMelanocortinsPCSK1 protein, humanPro-OpiomelanocortinProprotein Convertase 1Receptor, Melanocortin, Type 4Receptors, Leptingenetic obesitypersonalized medicinesetmelanotidesyndromic obesity

Identifiers

PMID41451896
PMCPMC12850549

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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.