{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T16:38:13Z","timestamp":1772555893768,"version":"3.50.1"},"reference-count":24,"publisher":"American Academy of Pediatrics (AAP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVES:<\/jats:title>\n                  <jats:p>Cornelia de Lange syndrome (CdLS) is a genetic syndrome with multisystem abnormalities. Infections are a significant cause of morbidity and mortality. The goals of our study were to identify the frequency and types of infections in CdLS and to determine if underlying immunodeficiency contributes to the clinical spectrum of this syndrome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS:<\/jats:title>\n                  <jats:p>We assessed infectious histories in 45 patients with CdLS and evaluated conventional immunologic screening tests in 27 patients. Among these 27 subjects, additional phenotypic enumeration of T-cell subsets, expression of activation markers in T cells, and production of cytokines in response to T-cell stimulants were studied in 12 CdLS subjects compared with 12 normal case control subjects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS:<\/jats:title>\n                  <jats:p>Recurrent infections were reported at high frequency in CdLS patients and included chronic ear infections (53%), chronic viral respiratory infections (46%), pneumonia (42%), sinus infections (33%), oral candidiasis (13%), sepsis (6%), and bacterial skin infections (4%). Full immune evaluation in 27 subjects led to identification of 9 cases of antibody deficiency syndrome in patients with severe forms of CdLS. Subjects with CdLS had decreased percentages of T regulatory cells and T follicular helper cells compared with normal control subjects (P &amp;lt; .05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS:<\/jats:title>\n                  <jats:p>This study identified for the first time a high frequency of antibody deficiency in CdLS subjects, indicating a critical need for screening and management of immunodeficiency in CdLS patients with a history of well-documented severe or recurrent infections. Furthermore, our results indicate that impaired T-cell populations may be associated with antibody deficiency in CdLS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1542\/peds.2012-3815","type":"journal-article","created":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T00:46:43Z","timestamp":1372726003000},"page":"e484-e489","source":"Crossref","is-referenced-by-count":34,"title":["Immunologic Features of Cornelia de Lange Syndrome"],"prefix":"10.1542","volume":"132","author":[{"given":"Soma","family":"Jyonouchi","sequence":"first","affiliation":[{"name":"Divisions of Allergy and Immunology and"},{"name":"Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan","family":"Orange","sequence":"additional","affiliation":[{"name":"Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics, Texas Children\u2019s Hospital, Houston, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen E.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Divisions of Allergy and Immunology and"},{"name":"Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Krantz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and"},{"name":"Genetics, The Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Deardorff","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and"},{"name":"Genetics, The Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[2013,8,1]]},"reference":[{"issue":"12","key":"2021120900153246100_B1","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1002\/ajmg.a.31757","article-title":"Cornelia de Lange syndrome: clinical review, diagnostic and scoring systems, and anticipatory guidance.","volume":"143A","author":"Kline","year":"2007","journal-title":"Am J Med Genet A"},{"issue":"12","key":"2021120900153246100_B2","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1002\/ajmg.a.34329","article-title":"Causes of death and autopsy findings in a large study cohort of individuals with Cornelia de Lange syndrome and review of the literature.","volume":"155A","author":"Schrier","year":"2011","journal-title":"Am J Med Genet A"},{"issue":"6","key":"2021120900153246100_B3","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/ng1364","article-title":"Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.","volume":"36","author":"Krantz","year":"2004","journal-title":"Nat Genet"},{"issue":"6","key":"2021120900153246100_B4","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/ng1363","article-title":"NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.","volume":"36","author":"Tonkin","year":"2004","journal-title":"Nat Genet"},{"issue":"3","key":"2021120900153246100_B5","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jaci.2007.05.042","article-title":"Risk of developing asthma in young children with atopic eczema: a systematic review.","volume":"120","author":"van der Hulst","year":"2007","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"2021120900153246100_B6","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.ajhg.2012.04.019","article-title":"RAD21 mutations cause a human cohesinopathy.","volume":"90","author":"Deardorff","year":"2012","journal-title":"Am J Hum Genet"},{"issue":"7415","key":"2021120900153246100_B7","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nature11316","article-title":"HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.","volume":"489","author":"Deardorff","year":"2012","journal-title":"Nature"},{"issue":"2","key":"2021120900153246100_B8","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.gde.2011.01.018","article-title":"Cohesin: genomic insights into controlling gene transcription and development.","volume":"21","author":"Dorsett","year":"2011","journal-title":"Curr Opin Genet Dev"},{"issue":"7180","key":"2021120900153246100_B9","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/nature06634","article-title":"Cohesin mediates transcriptional insulation by CCCTC-binding factor.","volume":"451","author":"Wendt","year":"2008","journal-title":"Nature"},{"issue":"12","key":"2021120900153246100_B10","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1093\/hmg\/ddm098","article-title":"Increased DNA damage sensitivity of Cornelia de Lange syndrome cells: evidence for impaired recombinational repair.","volume":"16","author":"Vrouwe","year":"2007","journal-title":"Hum Mol Genet"},{"issue":"4","key":"2021120900153246100_B11","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.it.2012.02.004","article-title":"Cohesin, CTCF and lymphocyte antigen receptor locus rearrangement.","volume":"33","author":"Seitan","year":"2012","journal-title":"Trends Immunol"},{"issue":"5","key":"2021120900153246100_B12","doi-asserted-by":"crossref","first-page":"e1000119","DOI":"10.1371\/journal.pbio.1000119","article-title":"Transcriptional dysregulation in NIPBL and cohesin mutant human cells.","volume":"7","author":"Liu","year":"2009","journal-title":"PLoS Biol"},{"issue":"11","key":"2021120900153246100_B13","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/nri2644","article-title":"New insights into the differentiation and function of T follicular helper cells.","volume":"9","author":"King","year":"2009","journal-title":"Nat Rev Immunol"},{"issue":"6","key":"2021120900153246100_B14","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nri1632","article-title":"NFAT proteins: key regulators of T-cell development and function.","volume":"5","author":"Macian","year":"2005","journal-title":"Nat Rev Immunol"},{"issue":"3","key":"2021120900153246100_B15","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S0022-3476(97)70200-2","article-title":"Immunophenotyping of blood lymphocytes in childhood. Reference values for lymphocyte subpopulations.","volume":"130","author":"Comans-Bitter","year":"1997","journal-title":"J Pediatr"},{"issue":"2","key":"2021120900153246100_B16","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.iac.2008.01.001","article-title":"Common variable immunodeficiency: an update on etiology and management.","volume":"28","author":"Yong","year":"2008","journal-title":"Immunol Allergy Clin North Am"},{"issue":"10","key":"2021120900153246100_B17","doi-asserted-by":"crossref","first-page":"5556","DOI":"10.4049\/jimmunol.1002828","article-title":"CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses.","volume":"186","author":"Chevalier","year":"2011","journal-title":"J Immunol"},{"issue":"1","key":"2021120900153246100_B18","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.immuni.2010.12.012","article-title":"Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion.","volume":"34","author":"Morita","year":"2011","journal-title":"Immunity"},{"issue":"5","key":"2021120900153246100_B19","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.jaci.2009.03.030","article-title":"TH17 cells and regulatory T cells in primary immunodeficiency diseases.","volume":"123","author":"Ochs","year":"2009","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"2021120900153246100_B20","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1001\/archderm.140.4.466","article-title":"Dermatologic and immunologic findings in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.","volume":"140","author":"Nieves","year":"2004","journal-title":"Arch Dermatol"},{"issue":"6","key":"2021120900153246100_B21","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.jaci.2008.09.037","article-title":"Omenn syndrome: inflammation in leaky severe combined immunodeficiency.","volume":"122","author":"Villa","year":"2008","journal-title":"J Allergy Clin Immunol"},{"issue":"1","key":"2021120900153246100_B22","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.clim.2007.02.001","article-title":"Impaired in vitro regulatory T cell function associated with Wiskott-Aldrich syndrome.","volume":"124","author":"Adriani","year":"2007","journal-title":"Clin Immunol"},{"issue":"1","key":"2021120900153246100_B23","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/ajmg.a.33631","article-title":"The incidence of thrombocytopenia in children with Cornelia de Lange syndrome.","volume":"155A","author":"Lambert","year":"2011","journal-title":"Am J Med Genet A"},{"issue":"7361","key":"2021120900153246100_B24","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nature10312","article-title":"A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation.","volume":"476","author":"Seitan","year":"2011","journal-title":"Nature"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/132\/2\/e484\/1091578\/peds_2012-3815.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/132\/2\/e484\/1091578\/peds_2012-3815.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T05:48:34Z","timestamp":1639028914000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/132\/2\/e484\/31398\/Immunologic-Features-of-Cornelia-de-Lange-Syndrome"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,1]]},"references-count":24,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2013,8,1]]},"published-print":{"date-parts":[[2013,8,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2012-3815","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,1]]}}}