Evidence map›Paper›PMID 41535479›Full record

ArticleEuropean journal of human genetics : EJHG2026

Pleiotropic genes linking congenital hypogonadotropic hypogonadism and cleft lip/palate: evidence from a genomic CHH cohort study.

Fernanda de Azevedo Correa, Imen Habibi, Jing Zhai, Michela Adamo, Yi Wang, Alexia Boizot, Yassine Zouaghi, Anita Rauch, Sandra Pekic, Richard Quinton and 15 more

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In one paragraph

Article in European journal of human genetics : EJHG, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Fernanda de Azevedo CorreaDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.ORCID 0000-0003-2107-9494
Imen HabibiDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
Jing ZhaiDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
Michela AdamoDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.ORCID 0000-0002-9994-0945
Yi WangDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
Alexia BoizotFaculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Yassine ZouaghiDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
Anita RauchInstitute of Medical Genetics, University of Zurich, Zurich, Switzerland.ORCID 0000-0003-2930-3163
Sandra PekicDepartment of Neuroendocrinology, Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Faculty of Medicine, University Clinical Center, University of Belgrade, Beograd, Serbia.
Richard QuintonDepartment of Metabolism, Digestion & Reproduction, Imperial College London, London, UK.
Marco BonomiDepartment of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Biagio CangianoDepartment of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Waljit S DhilloSection of Endocrinology and Investigative Medicine, Imperial College London, London, UK.
Christa E FluckDivision of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Bern University Hospital, University of Bern, Bern, Switzerland.
Attila NemethDepartment of Endocrinology, St John's Hospital, Budapest, Hungary.
Pierre-Marc BoulouxCenter for Neuroendocrinology, Royal Free Campus, University College Medical School, London, UK.
Jean-Marc FerraraRue du Curtil-Maillet Yverdon-les-Bains, Yverdon-les-Bains, Switzerland.
Duarte PignatelliDepartment of Endocrinology, Hospital S João, Porto, Portugal.
Zita HalászBókay Street Department, Paediatric Centre, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Cecilia Perdices-LopezDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
Andrea MessinaDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
Nicolas J NiederländerDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
Federico SantoniDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
James S AciernoDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
Nelly PitteloudDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland. nelly.pitteloud@chuv.ch.ORCID 0000-0003-0971-3237

Funding

DH | National Institute for Health Research (NIHR) NIHR202371Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) IZCOZ0_182958
6 · The paper itself

Abstract

Congenital hypogonadotropic hypogonadism (CHH) is a rare and genetically heterogeneous disorder characterized by absent or incomplete puberty due to impaired gonadotropin-releasing hormone (GnRH) function. A subset of individuals with CHH also present with developmental anomalies, including midline defects such as cleft lip and/or palate (CLP). This study investigates the genetic overlap between CHH and CLP. A total of 336 individuals diagnosed with CHH were clinically assessed for associated phenotypes, including CLP. High-throughput sequencing was performed using a targeted gene panel encompassing known CHH- and CLP-related genes. Variants were analyzed and classified according to the American College of Medical Genetics and Genomics (ACMG) criteria for pathogenicity. CLP was present in 21 patients with CHH (6%). Pathogenic or likely pathogenic variants in genes associated with both CHH and CLP-such as FGFR1 and CHD7-were identified in eight individuals. Furthermore, 17% of the patients with CHH without CLP harbored deleterious variants in genes implicated in clefting, including DVL3, PLCB4, NIPBL, and EDNRA. Evidence of digenic inheritance involving both CHH- and CLP-related genes was observed in multiple cases. FGFR1 variants were the most frequently detected and were commonly associated with anosmia and additional developmental anomalies. These findings highlight a genetic and phenotypic continuum between CHH and CLP, underscoring the involvement of shared developmental pathways. The high prevalence of FGFR1 variants in patients with CHH and CLP supports its role as a pleiotropic gene. Understanding the overlapping genetic mechanisms may enhance diagnostic precision and inform personalized management strategies for affected individuals.

Indexed as

Cleft LipCleft PalateGenetic PleiotropyHypogonadismAdolescentChildChild, PreschoolCohort StudiesDNA-Binding ProteinsDNA HelicasesFemaleHumansMalePhenotypeReceptor, Fibroblast Growth Factor, Type 1CHD7 protein, humanDNA-Binding ProteinsDNA HelicasesFGFR1 protein, humanReceptor, Fibroblast Growth Factor, Type 1

Identifiers

PMID41535479
PMCPMC12963409

What Socratic 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 Socratic graph.