{ "abstract": "RAG1/RAG2 deficiency causes diverse SCID phenotypes, but large, systematically characterized cohorts from North Africa remain lacking. We retrospectively characterized 128 confirmed RAG1/RAG2-deficient patients diagnosed over 14 years in Algeria, classified per PIDTC 2022 criteria. Consanguinity was high (70.3%), with RAG2 (57.0%) outnumbering RAG1 (43.0%), a reversal of patterns reported elsewhere. Classical SCID (61.0%) and Omenn syndrome (23.4%) predominated. Two candidate founder variants (RAG1 c.519del, RAG2 c.104G>T) accounted for 76.6% of genotypes, yet identical c.519del genotypes produced three discordant phenotypes. Four novel variants and four digenic/oligogenic cases broadened the molecular spectrum. Despite a short diagnostic delay, mortality was 89.1%, driven primarily by near-absent HSCT access (2.3%). This study expands the molecular and clinical spectrum of RAG deficiency in an underrepresented population, revealing a reversed RAG1/RAG2 ratio and phenotypic heterogeneity despite shared founder genotypes. These findings prioritize functional validation of uncertain-significance variants and underscore the need for NBS and expanded transplant access to translate diagnosis into survival.", "abstract_shown": true, "affiliations": [ "Department of Immunology, Beni Messous University Hospital Center, Algiers, Algeria.", "Faculty of Pharmacy, University of Health Sciences , Algiers, Algeria.", "Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.", "Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.", "National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.", "Department of Pediatrics, Setif University Hospital Center, Faculty of Medicine, The University of Setif 1, Setif, Algeria.", "Department of Pediatric Pulmonology and Allergology, Canastel Children's Hospital, Faculty of Medicine, The University of Oran, Oran, Algeria.", "Department of Pediatrics A, Beni Messous University Hospital Center, Algiers, Algeria.", "Faculty of Medicine, University of Health Sciences , Algiers, Algeria.", "Central Laboratory, Zeralda Burn Hospital , Algiers, Algeria.", "Department of Pediatrics B, Beni Messous University Hospital Center, Algiers, Algeria.", "Department of Pediatrics, Bab El Oued University Hospital Center, Algiers, Algeria.", "Department of Pediatrics, Bejaia University Hospital Center, Faculty of Medicine, The University of Bejaia, Bejaia, Algeria.", "Department of Pediatrics B, Hussein Dey University Hospital Center, Algiers, Algeria.", "Department of Pediatrics, Bologhine Hospital, Algiers, Algeria.", "Department of Pediatrics, Birtraria Hospital, Algiers, Algeria.", "Department of Pediatrics, Beni Messous Military Mother and Child Hospital, Algiers, Algeria.", "Department of Pediatrics, Specialized Mother and Child Hospital of Tlemcen, Tlemcen, Algeria.", "Faculty of Medicine, University of Tlemcen, Tlemcen, Algeria.", "Department of Pediatrics, El Oued Hospital, El Oued, Algeria.", "Department of Pediatrics, Thenia Hospital, Boumerdes, Algeria.", "Department of Pediatrics, Ouargla Hospital, Ouargla, Algeria.", "Department of Pediatrics, Djelfa Hospital, Djelfa, Algeria.", "Department of Pediatrics, Merouana Hospital, Batna, Algeria.", "Department of Pediatrics, Boussaada Hospital, Boussaada, Algeria.", "Department of Neonatology, Mother and Child Specialized Hospital of Batna, Algeria.", "Faculty of Medicine, The University of Batna, Algeria.", "Department of Pediatrics, Batna University Hospital Center, Batna, Algeria.", "Department of Pediatrics, Sidi Bel Abbes University Hospital Center, Faculty of Medicine, The University of Sidi Bel Abbes, Sidi Bel Abbes, Algeria.", "Department of Pediatrics B, University Hospital of Constantine, Faculty of Medicine, The University of Constantine 3, Constantine, Algeria.", "Department of Pediatrics, Tizi Ouzou University Hospital Center, Faculty of Medicine, the University of Tizi Ouzou, Tizi Ouzou, Algeria.", "Department of Hematology and Bone Morrow Transplantation, Pierre and Marie Curie Center, Algiers, Algeria.", "Department of Pediatrics A, Hussein Dey University Hospital Center, Algiers, Algeria.", "Department of Pediatrics, Tlemcen University Hospital Center, Tlemcen, Algeria.", "Department of Pediatrics, Mustapha Bacha University Hospital Center, Algiers, Algeria." ], "article_type": "research article", "arxiv": null, "author_total": 68, "authors": [ { "affs": [ 0, 1 ], "name": "Brahim Belaid", "orcid": "0000-0001-7618-4051" }, { "affs": [ 2 ], "name": "Koon-Wing Chan", "orcid": "0000-0001-9069-4568" }, { "affs": [ 3 ], "name": "Jennifer Stoddard", "orcid": "0000-0002-2137-9158" }, { "affs": [ 3 ], "name": "Julie Niemela", "orcid": "0000-0003-4197-3792" }, { "affs": [ 4 ], "name": "Heather Kenney", "orcid": "0009-0006-7009-2547" }, { "affs": [ 3 ], "name": "Adriana A De Jesus", "orcid": "0000-0001-8966-8362" }, { "affs": [ 2 ], "name": "Daniel Leung", "orcid": "0000-0002-9360-6233" }, { "affs": [ 2 ], "name": "Jing Yang", "orcid": "0000-0002-2405-8990" }, { "affs": [ 2 ], "name": "Xing Tian Yang", "orcid": "0000-0002-8849-0782" }, { "affs": [ 5 ], "name": "Abdelhak Dehimi", "orcid": "0009-0009-0136-3667" }, { "affs": [ 6 ], "name": "Ouardia Drali", "orcid": "0000-0002-8796-662X" }, { "affs": [ 7, 8 ], "name": "Aida Mohand Oussaid", "orcid": "0009-0000-1386-6266" }, { "affs": [ 0, 1 ], "name": "Lydia Lamara Mahammed", "orcid": "0000-0002-5360-8066" }, { "affs": [ 0, 1 ], "name": "Lilya Meriem Berkani", "orcid": "0000-0001-9456-5114" }, { "affs": [ 0 ], "name": "Hassiba Sakhri", "orcid": "0009-0007-8724-4890" }, { "affs": [ 0 ], "name": "Asmaa Abed", "orcid": "0009-0003-1632-4018" }, { "affs": [ 0 ], "name": "Meriem Tahir", "orcid": "0009-0009-8929-874X" }, { "affs": [ 0, 1 ], "name": "Fatma Merah", "orcid": "0009-0008-9287-4886" }, { "affs": [ 0, 1 ], "name": "Alaa Hamidou Benmoussa", "orcid": "0009-0001-9186-7376" }, { "affs": [ 1, 9 ], "name": "Ines Allam", "orcid": "0000-0001-6399-9593" }, { "affs": [ 0 ], "name": "Lylia Djidjeli", "orcid": "0009-0005-3130-9929" }, { "affs": [ 0 ], "name": "Hadia Boussaha", "orcid": "0009-0005-5549-0814" }, { "affs": [ 8, 10 ], "name": "Amina Salmi", "orcid": "0009-0009-5382-391X" }, { "affs": [ 8, 10 ], "name": "Sonia Yasmine Kirane", "orcid": "0009-0008-3158-2724" }, { "affs": [ 7, 8 ], "name": "Radia Rezzak", "orcid": "0009-0008-0920-2262" }, { "affs": [ 7, 8 ], "name": "Fella Lamrani", "orcid": "0009-0005-9460-2751" }, { "affs": [ 8, 11 ], "name": "Souhila Melzi", "orcid": "0009-0003-2682-8308" }, { "affs": [ 12 ], "name": "Fella Dahmoune", "orcid": "0009-0004-4826-8644" }, { "affs": [ 8, 13 ], "name": "Fairouz Guerrouche", "orcid": "0009-0001-2406-678X" }, { "affs": [ 13 ], "name": "Ahlem Mechali", "orcid": "0009-0003-9275-5610" }, { "affs": [ 8, 14 ], "name": "Amina Saad Djaballah", "orcid": "0009-0009-8322-5582" }, { "affs": [ 8, 15 ], "name": "Lamia Amirat", "orcid": "0009-0009-8646-8731" }, { "affs": [ 6 ], "name": "Meriem Oussalah", "orcid": "0009-0002-5767-4332" }, { "affs": [ 8, 16 ], "name": "Yacine Inouri", "orcid": "0009-0002-8555-4450" }, { "affs": [ 17, 18 ], "name": "Saadeddine Dib", "orcid": "0009-0002-2298-1957" }, { "affs": [ 17 ], "name": "Fatima Benbida", "orcid": "0009-0008-3339-3468" }, { "affs": [ 19 ], "name": "Amara Zelaci", "orcid": "0009-0001-4209-7803" }, { "affs": [ 20 ], "name": "Mohamed Amine Ifri", "orcid": "0009-0008-2396-2305" }, { "affs": [ 21 ], "name": "Kawthar Allali", "orcid": "0009-0001-9563-8300" }, { "affs": [ 22 ], "name": "Seddam Hocin Gafazi", "orcid": "0009-0000-8311-6639" }, { "affs": [ 23 ], "name": "Sara Makhloufi", "orcid": "0009-0009-5968-6071" }, { "affs": [ 24 ], "name": "Houda Larkat", "orcid": "0009-0005-7200-6983" }, { "affs": [ 25, 26 ], "name": "Fadela Bendaoud", "orcid": "0009-0002-2720-8525" }, { "affs": [ 26, 27 ], "name": "Noui Djamila", "orcid": "0009-0009-9727-7615" }, { "affs": [ 7, 8 ], "name": "Hamza Boucenna", "orcid": "0000-0001-7283-1151" }, { "affs": [ 28 ], "name": "Khadidja Benallal", "orcid": "0009-0008-2551-0644" }, { "affs": [ 17, 18 ], "name": "Chahrazed El Mezouar", "orcid": "0009-0005-8961-6753" }, { "affs": [ 29 ], "name": "Samia Bicha", "orcid": "0009-0000-7647-5019" }, { "affs": [ 29 ], "name": "Rachid Bouhdjila", "orcid": "0009-0000-2013-4258" }, { "affs": [ 30 ], "name": "Nadia Bensaadi", "orcid": "0009-0005-1451-2132" }, { "affs": [ 8, 31 ], "name": "Farih Mehdid", "orcid": "0009-0008-7437-0510" }, { "affs": [ 8, 31 ], "name": "Malek Benakli", "orcid": "0000-0001-8444-890X" }, { "affs": [ 8, 11 ], "name": "Rawda Aboura", "orcid": "0009-0006-8563-6535" }, { "affs": [ 8, 32 ], "name": "Zoulikha Zeroual", "orcid": "0009-0003-1689-2701" }, { "affs": [ 8, 14 ], "name": "Leila Smati", "orcid": "0009-0001-4907-0259" }, { "affs": [ 18, 33 ], "name": "Salih Bendeddouche", "orcid": "0009-0002-5483-7394" }, { "affs": [ 8, 34 ], "name": "Reda Belbouab", "orcid": "0000-0001-8461-7697" }, { "affs": [ 8, 13 ], "name": "Azzeddine Mekki", "orcid": "0009-0001-8855-706X" }, { "affs": [ 5 ], "name": "Belkacem Bioud", "orcid": "0009-0008-3716-0434" }, { "affs": [ 8, 15 ], "name": "Samir Mohamed Ladj", "orcid": "0009-0002-0510-3933" } ], "bibtex": "https://research.draconitic.com/paper/ct3kw0bkzgafa.bib", "cited_by": 0, "doi": "10.70962/jhi.20260168", "fulltext_url": "https://europepmc.org/articles/PMC13701135", "id": "ct3kw0bkzgafa", "issns": [ "3065-8993" ], "landing_url": "https://europepmc.org/article/MED/42929759", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "lcc", "RC581-607" ], [ "openalex", "2403|Immunodeficiency and Autoimmune Disorders" ] ], "openalex": "W7223705734", "pdf_url": "https://europepmc.org/articles/PMC13701135?pdf=render", "pmcid": "PMC13701135", "pmid": "42929759", "published": "2026-10-26", "publisher": "Rockefeller University Press", "ris": "https://research.draconitic.com/paper/ct3kw0bkzgafa.ris", "sources": [ { "first_seen": "2026-10-30T12:21:51Z", "native_id": "MED:42929759", "source": "europepmc", "url": "https://europepmc.org/article/MED/42929759" }, { "first_seen": "2026-10-31T14:21:14Z", "native_id": "089846e3d7c04458bbb9024c882f5b4b", "source": "doaj", "url": "https://doi.org/10.70962/jhi.20260168" } ], "subjects": [ { "field": "biology", "origin": "openalex:2403|Immunodeficiency and Autoimmune Disorders", "subfield": "immunology" } ], "title": "The genetic landscape of RAG deficiency: Novel and founder variants in a large Algerian cohort.", "title_text": "The genetic landscape of RAG deficiency: Novel and founder variants in a large Algerian cohort.", "type": "peer-reviewed", "updated_at": "2026-10-31T14:21:14Z", "url": "https://research.draconitic.com/paper/ct3kw0bkzgafa", "venue": "Journal of human immunity", "versions": [] }