Evidence map›Paper›PMID 39578275›Full record

ArticleJournal of clinical immunology2024

2q33 Deletions Underlying Syndromic and Non-syndromic CTLA4 Deficiency.

Charlyne Brakta, Anne-Claude Tabet, Mathilde Puel, Mathilde Pacault, Marie-Claude Stolzenberg, Claire Goudet, Marguerite Merger, Héloïse Reumaux, Nathalie Lambert, Najiba Alioua and 27 more

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Article in Journal of clinical immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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  4. A novelFrontiers in immunology · 2025
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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

37 authors.

Charlyne BraktaStudy Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, EU, France.
Anne-Claude TabetGenetics Department, AP-HP, Robert-Debré University Hospital, Paris, EU, France.
Mathilde PuelStudy Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, EU, France.
Mathilde PacaultGenetics Department, AP-HP, Robert-Debré University Hospital, Paris, EU, France.
Marie-Claude StolzenbergLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, UMR 1163, Imagine Institute, INSERM, Paris, EU, France.
Claire GoudetPediatric Hematology Department, Timone Enfant, Assistance Publique Hôpitaux de Marseille (AP-HM), Marseille, EU, France.
Marguerite MergerDepartment of Internal Medicine and Clinical Immunology, University of Lille, Lille, EU, France.
Héloïse ReumauxPediatric Rheumatology Unit, Jeanne de Flandre Hospital, University of Lille, Lille, EU, France.
Nathalie LambertStudy Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, EU, France.
Najiba AliouaStudy Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, EU, France.
Valérie MalanInserm U1163, Imagine Institute, University of Paris Cité, Paris, Paris, EU, France.
Sylvain HaneinBioinformatic Platform, Institute of Genetic Diseases, Université Paris-Cité and Structure Fédérative de Recherche Necker, INSERM UMR1163, Imagine, Paris, EU, France.
Delphine Dupin-DeguineMedical Genetics Department, University of Toulouse, CHU Purpan, Toulouse, EU, France.
Emmanuel TreinerFaculty of Medicine, University Toulouse III Paul Sabatier, Toulouse, France.
Guillaume LefèvreInstitute for Translational Research in Inflammation (INFINITE), Inserm U1286, University of Lille, Lille, EU, France.
Méryem-Maud FarhatDepartment of Internal Medicine and Clinical Immunology, University of Lille, Lille, EU, France.
Luminita Elena LucaDepartment of Internal Medicine, Infectious and Tropical Diseases, University Hospital Center of Poitiers, Poitiers, EU, France.
Marguerite HureauxDepartment of Genetics, Georges-Pompidou European Hospital, AP-HP, Paris, EU, France.
Hailun LiInserm U1163, Imagine Institute, University of Paris Cité, Paris, Paris, EU, France.
Nora ChellougMedical Genetics Department, University of Toulouse, CHU Purpan, Toulouse, EU, France.
Rabha DehakDepartment of Pediatrics, Calais Hospital, Calais, EU, France.
Simon BoussionClinical Genetics Department, University of Lille, Lille, EU, France.
Marie Ouachée-ChardinDepartment of Pediatric Hematology, IHOPe, Hospices Civils de Lyon, Lyon, EU, France.
Nicolas SchleinitzDepartment of Internal Medicine La Timone, Aix-Marseille University, Assistance Publique - AP-HM, Marseille, EU, France.
Wadih Abou ChahlaDepartment of Pediatric Hematology, Jeanne de Flandre Hospital, University of Lille, Lille, EU, France.
Vincent BarlogisPediatric Hematology Department, Timone Enfant, Assistance Publique Hôpitaux de Marseille (AP-HM), Marseille, EU, France.
Frédéric VélyAix Marseille Université, CNRS, Inserm, Centre d'Immunologie de Marseille-Luminy, Marseille, EU, France.
Eric OksenhendlerClinical Immunology Department, Saint-Louis Hospital, Paris-Diderot University, Paris, EU, France.
Pierre QuartierPediatric Immunology-Hematology and Rheumatology Unit, Necker-Enfants Malades University Hospital, AP-HP, Paris, EU, France.
Marlène PasquetDepartment of Pediatric Hematology and Immunology, Children's Hospital, University Hospital, Toulouse, EU, France.
Felipe SuarezUniversité Paris-Cité, Paris, EU, France.
Jacinta BustamanteStudy Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, EU, France.
Bénédicte NevenLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, UMR 1163, Imagine Institute, INSERM, Paris, EU, France.
Capucine PicardStudy Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, EU, France.
Frédéric Rieux-LaucatLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, UMR 1163, Imagine Institute, INSERM, Paris, EU, France.
Jonathan Lévy *Genetics Department, AP-HP, Robert-Debré University Hospital, Paris, EU, France.
Jérémie Rosain *Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, EU, France. jeremie.rosain@institutimagine.org.

Funding

Agence Nationale de la Recherche ANR-10-IAHU-01
6 · The paper itself

Abstract

purposeCTLA4 deficiency is an inborn error of immunity (IEI) due to heterozygosity for germline loss-of-function variants of the CTLA4 gene located on chromosome 2q33.2. CTLA4 deficiency underlies pleiotropic immune and lymphoproliferation-mediated features with incomplete penetrance. It has been identified in hundreds of patients but copy number variants (CNVs) have been reported in only 12 kindreds, including nine which displayed large 2q33.1-2q33.2 deletions encompassing CTLA4.

methodsWe conducted a nationwide study in France to identify patients with 2q33 deletions encompassing CTLA4. We investigated the clinical and immunological phenotypes and genotypes of these patients.

resultsWe identified 12 patients across six unrelated kindreds with clinical immunodeficiency. Neurological features were recorded in three patients, including one with syndromic neurodevelopmental disorder. Single-nucleotide polymorphism (SNP) or comparative genomic hybridization (CGH) array analysis, and targeted high-throughput sequencing revealed five different heterozygous 2q33 deletions of 26 kilobases to 7.12 megabases in size and encompassing one to 41 genes. We identified a contiguous gene syndrome (CGS) due to associated KLF7 deficiency in a kindred with a neurodevelopmental phenotype.

conclusionDeletions within the 2q33 region encompassing CTLA4 are rare and not extensively explored, and are probably underdiagnosed in cytogenetic practice. A literature review identified 14 different CGS loci including at least one gene responsible for an IEI. The deletions involved in IEIs should be systematically delimited, to facilitate screening for CGS.

Indexed as

Chromosomes, Human, Pair 2CTLA-4 AntigenAdolescentChildChild, PreschoolChromosome DeletionComparative Genomic HybridizationDNA Copy Number VariationsFemaleFranceGenetic Predisposition to DiseaseGenotypeHumansInfantMalePedigreeCTLA-4 AntigenCTLA4 protein, human2q33 deletionContiguous gene syndromeCopy number variationsCTLA4 (cytotoxic T lymphocyte-associated protein 4) deficiencyCytogeneticsKLF7

Identifiers

PMID39578275

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