{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:21:51Z","timestamp":1790461311245,"version":"4.1.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"The Promedica foundation"},{"name":"The Children's Research Centre of the University Children's Hospital of \u200eZurich \u200e"},{"name":"The Clinical Research Priority Program of the University of Zurich for the CRPP \u200eCYTIMM-Z"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Severe combined immunodeficiency (SCID) is fatal if not treated with immune reconstitution. In Egypt, T-B+ SCID accounts for 38\u00b75% of SCID diagnoses. An accurate genetic diagnosis is essential for choosing appropriate treatment modalities and for offering genetic counseling to the patient's family. The objectives of this study were to describe the clinical, immunological and molecular characteristics of a cohort of twenty Egyptian patients with T-B+ SCID. The initial diagnosis (based on clinical features and flow cytometry) was followed by molecular investigation (whole-exome sequencing). All patients had the classic clinical picture for SCID, including failure to thrive (n = 20), oral candidiasis (n = 17), persistent diarrhea (n = 14), pneumonia (n = 13), napkin dermatitis (n = 10), skin rash (n = 7), otitis media (n = 3) and meningitis (n = 2). The onset of manifestations was at the age of 2\u00b74\u00a0\u00b1\u00a01\u00b76 months and diagnosis at the age of 6\u00b77\u00a0\u00b1 \u00b75 months, giving a diagnostic delay of 4\u00b73 months. JAK3 gene variants were most frequent (n = 12) with three novel variants identified, followed by IL2R\u03b3 variants (n = 6) with two novel variants. IL7R\u03b1 and CD3\u03b5 variants were found once, with a novel variant each. T-B+NK\u2212 SCID accounted for approximately 90% of the Egyptian patients with T-B+SCID. Of these T-B+NK\u2212 SCID cases, 60% were autosomal recessive syndromes caused by JAK3 mutations and 30% were X-linked syndromes. It might be useful to sequence the JAK3 gene (i.e. targeted Sanger sequencing) in all T-B+ SCID patients, especially after X-linked SCID has been ruled out. Hence, no more than 10% of T-B+ SCID patients might require next-generation for a molecular diagnosis.<\/jats:p>","DOI":"10.1111\/cei.13536","type":"journal-article","created":{"date-parts":[[2020,10,11]],"date-time":"2020-10-11T08:02:16Z","timestamp":1602403336000},"page":"448-457","source":"Crossref","is-referenced-by-count":11,"title":["Whole-exome sequencing of T-B+ severe combined immunodeficiency in Egyptian infants, JAK3 predominance and novel variants"],"prefix":"10.1093","volume":"203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6244-0288","authenticated-orcid":false,"given":"R","family":"El Hawary","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Clinical Pathology Department, Cairo University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-3820","authenticated-orcid":false,"given":"S","family":"Meshaal","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Clinical Pathology Department, Cairo University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A A","family":"Mauracher","sequence":"additional","affiliation":[{"name":"Division of Immunology, University Children's Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Opitz","sequence":"additional","affiliation":[{"name":"ETH Zurich, Functional Genomics Center Z\u00fcrich, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Abd Elaziz","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Pediatrics Department, Cairo University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Lotfy","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Pediatrics Department, Cairo University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Eldash","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Clinical Pathology Department, Cairo University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Boutros","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Pediatrics Department, Cairo University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Galal","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Pediatrics Department, Cairo University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Pachlopnik Schmid","sequence":"additional","affiliation":[{"name":"Division of Immunology, University Children's Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Elmarsafy","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Pediatrics Department, Cairo University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"2021121023213611900_cei13536-bib-0001","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1182\/blood-2003-06-2104","article-title":"Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation","volume":"103","author":"Roberts","year":"2004","journal-title":"Blood"},{"key":"2021121023213611900_cei13536-bib-0002","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10875-010-9489-z","article-title":"Molecular diagnosis of severe combined immunodeficiency \u2013 identification of IL2RG, JAK3, IL7R, DCLRE1C, RAG1, and RAG2 mutations in a cohort of Chinese and Southeast Asian children","volume":"31","author":"Lee","year":"2011","journal-title":"J Clin Immunol"},{"key":"2021121023213611900_cei13536-bib-0003","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3389\/fimmu.2019.00023","article-title":"Clinical, immunological, and molecular findings in 57 patients with severe combined immunodeficiency (SCID) from India","volume":"10","author":"Aluri","year":"2019","journal-title":"Front Immunol"},{"key":"2021121023213611900_cei13536-bib-0004","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s40291-017-0297-5","article-title":"Genetic counseling in primary immunodeficiency disorders: an emerging experience in Egypt","volume":"21","author":"El Hawary","year":"2017","journal-title":"Mol Diagn Ther"},{"key":"2021121023213611900_cei13536-bib-0005","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.clim.2015.04.003","article-title":"Mutations in Recombination Activating Gene 1 and 2 in patients with severe combined immunodeficiency disorders in Egypt","volume":"158","author":"Meshaal","year":"2015","journal-title":"Clin Immunol"},{"key":"2021121023213611900_cei13536-bib-0006","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/pai.12179","article-title":"Modern management of primary T-cell immunodeficiencies","volume":"25","author":"Pachlopnik Schmid","year":"2014","journal-title":"Pediat Allerg Imm"},{"key":"2021121023213611900_cei13536-bib-0007","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s10875-016-0314-1","article-title":"Patterns of primary immunodeficiency disorders among a highly consanguineous population: Cairo University Pediatric Hospital's 5-year experience","volume":"36","author":"Galal","year":"2016","journal-title":"J Clin Immunol"},{"key":"2021121023213611900_cei13536-bib-0008","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1146\/annurev.immunol.22.012703.104614","article-title":"Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution","volume":"22","author":"Buckley","year":"2004","journal-title":"Annu Rev Immunol"},{"key":"2021121023213611900_cei13536-bib-0009","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.jaip.2018.07.046","article-title":"MHC-II deficiency among Egyptians: novel mutations and unique phenotypes","volume":"7","author":"El Hawary","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"2021121023213611900_cei13536-bib-0010","doi-asserted-by":"crossref","first-page":"e7989","DOI":"10.1097\/MD.0000000000007989","article-title":"Chronic active Epstein\u2013Barr virus infection as the initial symptom in a Janus kinase 3 deficiency child: case report and literature review","volume":"96","author":"Zhong","year":"2017","journal-title":"Medicine"},{"key":"2021121023213611900_cei13536-bib-0011","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.clim.2017.09.007","article-title":"Novel mutation in the JH4 domain of JAK3 causing severe combined immunodeficiency complicated by vertebral osteomyelitis","volume":"183","author":"Qamar","year":"2017","journal-title":"Clin Immunol"},{"key":"2021121023213611900_cei13536-bib-0012","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13223-018-0317-y","article-title":"IL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature","volume":"15","author":"Lim","year":"2019","journal-title":"Allergy Asthma Clin Immunol"},{"key":"2021121023213611900_cei13536-bib-0013","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s40124-014-0070-8","article-title":"The genetic and molecular basis of severe combined immunodeficiency","volume":"3","author":"Picard","year":"2015","journal-title":"Curr Pediatr Rep"},{"key":"2021121023213611900_cei13536-bib-0014","first-page":"1","article-title":"update on the classification from the international union of immunological societies expert committee","volume":"2020","author":"Tangye","year":"2019","journal-title":"J Clin Immunol"},{"key":"2021121023213611900_cei13536-bib-0015","author":"European Society for Immunodeficiencies"},{"key":"2021121023213611900_cei13536-bib-0016","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.jaci.2003.07.003","article-title":"Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study","volume":"112","author":"Shearer","year":"2003","journal-title":"J Allergy Clin Immunol"},{"key":"2021121023213611900_cei13536-bib-0017","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/j.jaip.2017.02.009","article-title":"Causes of low neonatal T-cell receptor excision circles: a systematic review","volume":"5","author":"Mauracher","year":"2017","journal-title":"J Allergy Clin Immunol Pract"},{"key":"2021121023213611900_cei13536-bib-0018","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.imlet.2019.10.001","article-title":"Genetic mutations and immunological features of severe combined immunodeficiency patients in Iran","volume":"216","author":"Shahbazi","year":"2019","journal-title":"Immunol Lett"},{"key":"2021121023213611900_cei13536-bib-0019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13104-018-3822-7","article-title":"Poliovirus excretion following vaccination with live poliovirus vaccine in patients with primary immunodeficiency disorders: clinicians\u2019 perspectives in the endgame plan for polio eradication","volume":"11","author":"Galal","year":"2018","journal-title":"BMC Res Notes"},{"key":"2021121023213611900_cei13536-bib-0020","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/mgg3.391","article-title":"JAK 3 mutations in Italian patients affected by SCID: new molecular aspects of a long-known gene","volume":"6","author":"Di Matteo","year":"2018","journal-title":"Mol Genet Genomic Med"},{"key":"2021121023213611900_cei13536-bib-0021","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1006\/clim.2000.4880","article-title":"Molecular modeling of the JAK3 kinase domains and structural basis for severe combined immunodeficiency","volume":"96","author":"Vihinen","year":"2000","journal-title":"Clin Immunol"},{"key":"2021121023213611900_cei13536-bib-0022","first-page":"1968","article-title":"Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency","volume":"89","author":"Puck","year":"1997","journal-title":"Blood"},{"key":"2021121023213611900_cei13536-bib-0023","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jmii.2018.02.003","article-title":"A novel pathogenic mutation on Interleukin-7 receptor leading to severe combined immunodeficiency identified with newborn screening and whole exome sequencing","volume":"53","author":"Liao","year":"2020","journal-title":"J Microbiol Immunol Infect"},{"key":"2021121023213611900_cei13536-bib-0024","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1111\/jdv.13888","article-title":"Unusual dermatological presentation and immune phenotype in SCID due to an IL7R mutation: the value of whole-exome sequencing and the potential benefit of newborn screening","volume":"31","author":"Marquardt","year":"2017","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"2021121023213611900_cei13536-bib-0025","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s00251-017-1005-7","article-title":"A novel pathogenic frameshift variant of CD3E gene in two T-B+ NK+ SCID patients from Turkey","volume":"69","author":"Firtina","year":"2017","journal-title":"Immunogenetics"},{"key":"2021121023213611900_cei13536-bib-0026","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1172\/JCI200422588","article-title":"Severe combined immunodeficiency caused by deficiency in either the \u03b4 or the \u03b5 subunit of CD3","volume":"114","author":"de Saint Basile","year":"2004","journal-title":"J Clin Invest"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cei.13536","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cei.13536","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/203\/3\/448\/41635124\/cei13536.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/203\/3\/448\/41635124\/cei13536.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T16:24:57Z","timestamp":1641054297000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/203\/3\/448\/6403217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,2]]},"references-count":26,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,11,2]]},"published-print":{"date-parts":[[2021,2,10]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.13536","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,3]]},"published":{"date-parts":[[2020,11,2]]}}}