{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:16:16Z","timestamp":1783016176253,"version":"3.54.6"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007045","name":"Secretar\u00eda de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n del Distrito Federal","doi-asserted-by":"publisher","award":["CBF\u20102023\u20102024\u2010376"],"award-info":[{"award-number":["CBF\u20102023\u20102024\u2010376"]}],"id":[{"id":"10.13039\/501100007045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016928","name":"Instituto Nacional de Pediatria","doi-asserted-by":"publisher","award":["2017\/010"],"award-info":[{"award-number":["2017\/010"]}],"id":[{"id":"10.13039\/100016928","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    CTLA\u20104 haploinsufficiency is caused by heterozygous variants in\n                    <jats:italic>CTLA4.<\/jats:italic>\n                    We report a cohort of five patients with a clinical presentation including immune dysregulation, hypogammaglobulinemia, lung damage, and gastrointestinal symptoms, consistent with CTLA\u20104 haploinsufficiency. Patients ranged from 10 to 23\u2009years of age, with three presenting before 7\u2009years. Immunoglobulin levels and lymphocyte subpopulations were evaluated. All the patients evaluated showed low levels of CTLA\u20104 and lymphoproliferation in unstimulated conditions. Treatment before genetic diagnosis consisted mainly of intravenous immunoglobulin replacement and pharmacological immunosuppression. Heterozygous variants in\n                    <jats:italic>CTLA4<\/jats:italic>\n                    were detected by exome sequencing. Immunological evaluation revealed reduced CTLA\u20104 expression and spontaneous lymphoproliferation. The identified heterozygous\n                    <jats:italic>CTLA4<\/jats:italic>\n                    variants included two novel variants, one previously classified as likely pathogenic, one as pathogenic, and one as a variant of uncertain significance. These findings expand the spectrum of\n                    <jats:italic>CTLA4<\/jats:italic>\n                    variants and support their clinical relevance.\n                  <\/jats:p>","DOI":"10.1111\/cge.70179","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T01:56:31Z","timestamp":1778032591000},"page":"260-267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Genetic Characteristics of Patients With Novel and Uncertain Significance Variants in\n                    <i>CTLA4<\/i>\n                    : A Mexican Cohort"],"prefix":"10.1111","volume":"110","author":[{"given":"Gabriela","family":"L\u00f3pez\u2010Herrera","sequence":"first","affiliation":[{"name":"Primary Immunodeficiencies Laboratory Instituto Nacional de Pediatr\u00eda  Mexico City Mexico"},{"name":"Departamento de Biolog\u00eda, Facultad de Qu\u00edmica UNAM  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"O'Farrill\u2010Romanillos","sequence":"additional","affiliation":[{"name":"Specialty Hospital, National Medical Center XXI Century  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Rodriguez\u2010Alba","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neurooncology Unit National Institute of Neurology and Neurosurgery  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noem\u00ed","family":"G\u00f3mez\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Allergy and Clinical Immunology Service, Unidad M\u00e9dica de Alta Especialidad, Centro M\u00e9dico Nacional de Occidente IMSS  Guadalajara Jalisco Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor G\u00f3mez\u2010Tello","family":"Hector","sequence":"additional","affiliation":[{"name":"Immunology Department Hospital para la ni\u00f1ez Poblana. IMSS Bienestar  Puebla Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Eunice","family":"Fregoso\u2010Z\u00fa\u00f1iga","sequence":"additional","affiliation":[{"name":"Children's Hospital of Morelia  Morelia Michoacan Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Antonio","family":"Yamazaki\u2010Nakashimada","sequence":"additional","affiliation":[{"name":"Clinical Immunology Department National Institute of Pediatrics  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Javier","family":"Espinosa\u2010Rosales","sequence":"additional","affiliation":[{"name":"Immunology, Allergy and Pediatrics Center, Angeles Lomas Hospital  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7726-1693","authenticated-orcid":false,"given":"Daniela","family":"P\u00e9rez\u2010P\u00e9rez","sequence":"additional","affiliation":[{"name":"Primary Immunodeficiencies Laboratory Instituto Nacional de Pediatr\u00eda  Mexico City Mexico"},{"name":"Departamento de Biolog\u00eda, Facultad de Qu\u00edmica UNAM  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3746"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40348\u2010023\u201000167\u20101"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.147.3.1037"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29061330"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.04.005"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13163"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1113"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad989"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1109\/ICCV.1999.790410"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410\u2010248"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010022\u201001352\u2010z"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.02.055"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3906\/sag\u20101511\u201067"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2016.07.236"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1255904"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0241903"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1052"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003819\u20102"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.24.021605.090535"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600682"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70179","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70179","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70179","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:19:51Z","timestamp":1783012791000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":21,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/cge.70179"],"URL":"https:\/\/doi.org\/10.1111\/cge.70179","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]},"assertion":[{"value":"2026-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}