{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:42:58Z","timestamp":1788982978575,"version":"build-2803163510"},"reference-count":64,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cVictor Babes\u201d University of Medicine and Pharmacy from Timisoara, Romania","award":["POSTDOC\/2020"],"award-info":[{"award-number":["POSTDOC\/2020"]}]},{"award":["POSTDOC\/2020"],"award-info":[{"award-number":["POSTDOC\/2020"]}],"id":[{"id":"https:\/\/ror.org\/00afdp487","id-type":"ROR","asserted-by":"publisher"}]},{"name":"patient association Asociatia Romana a Pacientilor cu Imunodeficiente Primare"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inborn errors of immunity (IEIs) encompass a heterogeneous group of more than 550 genetic conditions with variable ages of onset. A significant proportion of IEI arises from genetic variants that may not yet be fully elucidated or recorded in existing genomic databases. Molecular diagnoses are achieved in approximately 15\u201335% of IEI cases, yet in only 9\u201320% of individuals with predominant antibody deficiencies, particularly in adult cohorts. We aimed to evaluate whole genome sequencing (WGS) diagnostic yield in adults suspected to have IEI. Clinical assessments of the patients were carried out at tertiary medical institutions in Timisoara and Bucharest, Romania. The study cohort included a consecutive series of 21 adult patients (aged 19\u201360 years) with IEI phenotype, who underwent genetic analysis, using WGS as the first diagnostic approach. A definitive molecular diagnosis was confirmed in only 9.5% (2\/21) of the participants, in LRBA and BTK genes. Variants of uncertain significance (VUS) were detected in three patients (13.6%) in TNFRSF13B, COPA, GATA2 genes. For about half of the cohort the onset of the disease was noted in childhood. WGS as a first-line diagnostic strategy in a cohort of adults with IEI yielded a low diagnostic rate. There were significant delays in genetic diagnosis, as half of the cohort experienced childhood-onset symptoms. Results suggest that adult IEI diagnosis remains challenging, necessitating functional studies and longitudinal re-evaluation of genomic data.<\/jats:p>","DOI":"10.3390\/ijms27083415","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T12:01:52Z","timestamp":1775822512000},"page":"3415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Whole Genome Sequencing as First Diagnostic Approach for Inborn Errors of Immunity in Adults: Diagnostic Yield and Clinical Correlations"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2016-6620","authenticated-orcid":false,"given":"Cristina-Loredana","family":"Pantea","sequence":"first","affiliation":[{"name":"Regional Center of Medical Genetics Timis, Clinical Emergency Hospital for Children \u201cLouis Turcanu\u201d, Part of European Reference Network for Rare Malformation Syndromes, Intellectual and Other Neurodevelopmental Disorders (ERN-ITHACA), 300011 Timisoara, Romania"},{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Bataneant","sequence":"additional","affiliation":[{"name":"2nd Pediatric Department, Clinical Emergency Hospital for Children \u201cLouis Turcanu\u201d, 300011 Timisoara, Romania"},{"name":"Department of Pediatrics, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciprian","family":"Jurcut","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, \u201cDr. Carol Davila\u201d Central University Emergency Military Hospital, 010825 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Cochino","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020022 Bucharest, Romania"},{"name":"Department of Pediatrics, \u201cAlessandrescu Rusescu\u201d National Institute for Mother and Child Health, 020395 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8628-3352","authenticated-orcid":false,"given":"Andreea","family":"Ioan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, \u201cAlessandrescu Rusescu\u201d National Institute for Mother and Child Health, 020395 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8880-7501","authenticated-orcid":false,"given":"Catalin Vasile","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Regional Center of Medical Genetics Timis, Clinical Emergency Hospital for Children \u201cLouis Turcanu\u201d, Part of European Reference Network for Rare Malformation Syndromes, Intellectual and Other Neurodevelopmental Disorders (ERN-ITHACA), 300011 Timisoara, Romania"},{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2652-0931","authenticated-orcid":false,"given":"Cristian G.","family":"Zimbru","sequence":"additional","affiliation":[{"name":"Department of Automation and Applied Informatics, Politehnica University of Timisoara, 300006 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Urtila","sequence":"additional","affiliation":[{"name":"2nd Pediatric Department, Clinical Emergency Hospital for Children \u201cLouis Turcanu\u201d, 300011 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7554-4625","authenticated-orcid":false,"given":"Adela","family":"Chirita-Emandi","sequence":"additional","affiliation":[{"name":"Regional Center of Medical Genetics Timis, Clinical Emergency Hospital for Children \u201cLouis Turcanu\u201d, Part of European Reference Network for Rare Malformation Syndromes, Intellectual and Other Neurodevelopmental Disorders (ERN-ITHACA), 300011 Timisoara, Romania"},{"name":"Center of Genomic Medicine, Department of Microscopic Morphology, Genetics Discipline, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1016\/j.jaci.2024.01.011","article-title":"Validating inborn error of immunity prevalence and risk with nationally representative electronic health record data","volume":"153","author":"Rider","year":"2024","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Cortesi, M., Dotta, L., Cattalini, M., Lougaris, V., Soresina, A., and Badolato, R. (2024). Unmasking inborn errors of immunity: Identifying the red flags of immune dysregulation. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1497921"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.anai.2024.12.016","article-title":"Keeping up with recent developments in immunodeficiency","volume":"134","author":"Tsoulis","year":"2025","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yorulmaz, A., \u015eahin, A., Sonmez, G., Eldeniz, F.C., G\u00fcl, Y., Karaselek, M.A., G\u00fcler, \u015e.N., Kele\u015f, S., and Reisli, I. (2025). Enhancing the Prediction of Inborn Errors of Immunity: Integrating Jeffrey Modell Foundation Criteria with Clinical Variables Using Machine Learning. Children, 12.","DOI":"10.20944\/preprints202508.1174.v1"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13223-023-00862-8","article-title":"Inborn errors of immunity in adulthood","volume":"20","author":"Wang","year":"2024","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"von Hardenberg, S., Klefenz, I., Steinemann, D., Di Donato, N., Baumann, U., Auber, B., and Klemann, C. (2024). Current genetic diagnostics in inborn errors of immunity. Front. Pediatr., 12.","DOI":"10.3389\/fped.2024.1279112"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e20250002","DOI":"10.70962\/jhi.20250002","article-title":"The 2024 update of IUIS phenotypic classification of human inborn errors of immunity","volume":"1","author":"Bousfiha","year":"2025","journal-title":"J. Hum. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s10875-022-01289-3","article-title":"Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee","volume":"42","author":"Tangye","year":"2022","journal-title":"J. Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13223-024-00938-z","article-title":"Inborn errors of immunity (primary immunodeficiencies)","volume":"20","author":"Kim","year":"2025","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s12016-025-09103-9","article-title":"Immunodeficiencies in Adults: Key Considerations for Diagnosis and Management","volume":"68","author":"Regina","year":"2025","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_11","unstructured":"Sullivan, K.E., and Stiehm, E.R. (2020). Chapter 3\u2014Key pathways in primary immune deficiencies. Stiehm\u2019s Immune Deficiencies, Academic Press. [2nd ed.]. Available online: https:\/\/www.sciencedirect.com\/science\/article\/pii\/B978012816768700003X."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e20250007","DOI":"10.70962\/jhi.20250007","article-title":"Inborn errors of immunity: Manifestation, treatment, and outcome\u2014An ESID registry 1994\u20132024 report on 30,628 patients","volume":"1","author":"Kindle","year":"2025","journal-title":"J. Hum. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s10875-025-01947-2","article-title":"Whole Genome Sequencing in 25 Families with Suspected Inborn Errors of Immunity: Diagnostic Yield and Clinical Relevance of Genome-wide Analysis","volume":"45","author":"Lee","year":"2025","journal-title":"J. Clin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s12016-021-08838-5","article-title":"Next-Generation Sequencing in the Field of Primary Immunodeficiencies: Current Yield, Challenges, and Future Perspectives","volume":"61","author":"Vorsteveld","year":"2021","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.jaci.2022.06.009","article-title":"Clinical exome sequencing of 1000 families with complex immune phenotypes: Toward comprehensive genomic evaluations","volume":"150","author":"Similuk","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.jaci.2021.04.015","article-title":"Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations","volume":"148","author":"Thalhammer","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chovancova, Z., Hlavackova, E., Hakl, R., Milota, T., Kralickova, P., Malkusova, I., Hutyrova, B., Safarova, M., Vydlakova, J., and Jilek, D. (2025). First report from the Czech national registry of inborn errors of immunity (2012\u20132025). Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1653685"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.jaci.2015.02.040","article-title":"Clinical application of whole-genome sequencing in patients with primary immunodeficiency","volume":"136","author":"Mousallem","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"18830","DOI":"10.1038\/s41598-025-03492-9","article-title":"Genetic landscape of Romanian children with inborn errors of immunity via gene panels, exome, and genome sequencing","volume":"15","author":"Pantea","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/s41586-020-2265-1","article-title":"Whole-genome sequencing of a sporadic primary immunodeficiency cohort","volume":"583","author":"Thaventhiran","year":"2020","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s10875-018-0582-z","article-title":"Differing Performance of the Warning Signs for Immunodeficiency in the Diagnosis of Pediatric Versus Adult Patients in a Two-Center Tertiary Referral Population","volume":"39","author":"Bjelac","year":"2019","journal-title":"J. Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1586\/1744666X.2015.990440","article-title":"Important differences in the diagnostic spectrum of primary immunodeficiency in adults versus children","volume":"11","author":"Abolhassani","year":"2015","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Staels, F., Collignon, T., Betrains, A., Gerbaux, M., Willemsen, M., Humblet-Baron, S., Liston, A., Vanderschueren, S., and Schrijvers, R. (2021). Monogenic Adult-Onset Inborn Errors of Immunity. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.753978"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pieniawska-\u015amiech, K., Pasternak, G., Lewandowicz-Uszy\u0144ska, A., and Jutel, M. (2022). Diagnostic Challenges in Patients with Inborn Errors of Immunity with Different Manifestations of Immune Dysregulation. J. Clin. Med., 11.","DOI":"10.3390\/jcm11144220"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.jaci.2020.08.010","article-title":"Consensus of the Italian Primary Immunodeficiency Network on transition management from pediatric to adult care in patients affected with childhood-onset inborn errors of immunity","volume":"146","author":"Cirillo","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1111\/pai.13571","article-title":"Diverse clinical features and diagnostic delay in monogenic inborn errors of immunity: A call for access to genetic testing","volume":"32","author":"Branch","year":"2021","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s10875-024-01855-x","article-title":"Quantifying the Diagnostic Odyssey Burden Among Persons with Inborn Errors of Immunity","volume":"45","author":"Nikzad","year":"2025","journal-title":"J. Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1159\/000540538","article-title":"Delineating the Clinical and Immunologic Characteristics: A Comparative Study of Inborn Errors of Immunity in Adult versus Pediatric Diagnosed","volume":"185","author":"Karabiber","year":"2024","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Elsink, K., Huibers, M.M.H., Hollink, I.H.I.M., Simons, A., Zonneveld-Huijssoon, E., van der Veken, L.T., Leavis, H.L., Henriet, S.S.V., van Deuren, M., and van de Veerdonk, F.L. (2021). Implementation of Early Next-Generation Sequencing for Inborn Errors of Immunity: A Prospective Observational Cohort Study of Diagnostic Yield and Clinical Implications in Dutch Genome Diagnostic Centers. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.780134"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"del Pino-Molina, L., Bravo Gallego, L.Y., Soto Serrano, Y., Reche Yebra, K., Marty Lobo, J., Gonz\u00e1lez Mart\u00ednez, B., Garc\u00eda-Morato, M.B., Pena, R.R., van der Burg, M., and Granados, E.L. (2023). Research-based flow cytometry assays for pathogenic assessment in the human B-cell biology of gene variants revealed in the diagnosis of inborn errors of immunity: A Bruton\u2019s tyrosine kinase case-study. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1095123"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1016\/j.jaci.2025.07.017","article-title":"Hidden splice variants in inborn errors of immunity: Uncovering diagnoses and therapeutic targets","volume":"156","author":"Ochoa","year":"2025","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jaci.2019.09.009","article-title":"Diagnostic interpretation of genetic studies in patients with primary immunodeficiency diseases: A working group report of the Primary Immunodeficiency Diseases Committee of the American Academy of Allergy, Asthma & Immunology","volume":"145","author":"Chinn","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s10238-024-01392-2","article-title":"Diagnostic yield of next-generation sequencing in suspect primary immunodeficiencies diseases: A systematic review and meta-analysis","volume":"24","author":"Chen","year":"2024","journal-title":"Clin. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rozevska, M., Daila Neiburga-Vigante, K., Nartisa, I., Lucane, Z., Ozola, L., Bardina, L., Jaunalksne, I., Gerula, N., Krike, P., and Taurina, G. (2025). Genome and transcriptome sequencing for inborn errors of immunity: A feasible multi-omics diagnostic approach. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1510365"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1056\/NEJMoa2314761","article-title":"Genome Sequencing for Diagnosing Rare Diseases","volume":"390","author":"Wojcik","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/sji.12551","article-title":"Identification and Characterization of a Nationwide Danish Adult Common Variable Immunodeficiency Cohort","volume":"85","author":"Westh","year":"2017","journal-title":"Scand. J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8308","DOI":"10.1038\/s41598-021-87898-1","article-title":"The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID)","volume":"11","author":"Bisgin","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1002\/humu.23645","article-title":"ClinGen Variant Curation Expert Panel experiences and standardized processes for disease and gene-level specification of the ACMG\/AMP guidelines for sequence variant interpretation","volume":"39","author":"Milko","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1016\/j.jaci.2025.01.005","article-title":"Curation of gene\u2013disease relationships in primary antibody deficiencies using the ClinGen validation framework","volume":"155","author":"Ross","year":"2025","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lim, L.M., Chang, J.M., Wang, I.F., Chang, W.C., Hwang, D.Y., and Chen, H.C. (2013). Atypical X-linked agammaglobulinaemia caused by a novel BTK mutation in a selective immunoglobulin M deficiency patient. BMC Pediatr., 13.","DOI":"10.1186\/1471-2431-13-150"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.coi.2021.06.004","article-title":"TACI deficiency\u2014A complex system out of balance","volume":"71","author":"Salzer","year":"2021","journal-title":"Curr. Opin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/jmedgenet-2015-103690","article-title":"Genes associated with common variable immunodeficiency: One diagnosis to rule them all?","volume":"53","author":"Bogaert","year":"2016","journal-title":"J. Med Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"eLASID2025abstract.1","DOI":"10.70962\/LASID2025abstract.1","article-title":"Patient with Common Variable Immunodeficiency Type 2 Due to a Likely Pathogenic Mutation in the TNFRSF13B Gene, Carrier Mother","volume":"1","author":"Camacho","year":"2025","journal-title":"J. Hum. Immun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ajhg.2023.11.005","article-title":"Will variants of uncertain significance still exist in 2030?","volume":"111","author":"Fowler","year":"2024","journal-title":"Am. J. Hum. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Miguel Berenguel, L., Gianelli, C., Matas P\u00e9rez, E., del Rosal, T., M\u00e9ndez Echevarr\u00eda, A., Robles Marhuenda, \u00c1., Rodr\u00edguez, M.F., Molina, M.T.C., Garc\u00eda, L.M., and Garrido, B.S. (2025). Molecular assessment of splicing variants in a cohort of patients with inborn errors of immunity: Methodological approach and interpretation remarks. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1499415"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Immunology Task Force of the Italian Society of Pediatric Allergy and Immunology (SIAIP), Castagnoli, R., Lougaris, V., Giardino, G., Volpi, S., Leonardi, L., La Torre, F., Federici, S., Corrente, S., and Cinicola, B.L. (2021). Inborn errors of immunity with atopic phenotypes: A practical guide for allergists. World Allergy Organ. J., 14, 100513.","DOI":"10.1016\/j.waojou.2021.100513"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"ACMGSecondary Findings Working Group, Miller, D.T., Lee, K., Gordon, A.S., Amendola, L.M., Adelman, K., Bale, S.J., Chung, W.K., Gollob, M.H., and Harrison, S.M. (2021). Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: A policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet. Med., 23, 1391\u20131398.","DOI":"10.1038\/s41436-021-01171-4"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.jaci.2024.12.1075","article-title":"Update on inborn errors of immunity","volume":"155","author":"IJspeert","year":"2025","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Rudilla, F., Franco-Jarava, C., Mart\u00ednez-Gallo, M., Garcia-Prat, M., Mart\u00edn-Nalda, A., Rivi\u00e8re, J., Aguil\u00f3-Cucurull, A., Mongay, L., Vidal, F., and Solanich, X. (2019). Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing: Expected and Unexpected Findings. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02325"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"AB69","DOI":"10.1016\/j.jaci.2020.12.270","article-title":"Are we diagnosing too late? RAG deficiency in young adults with end organ damage","volume":"147","author":"Saco","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1007\/s10875-022-01276-8","article-title":"Copy Number Analysis in a Large Cohort Suggestive of Inborn Errors of Immunity Indicates a Wide Spectrum of Relevant Chromosomal Losses and Gains","volume":"42","author":"Wan","year":"2022","journal-title":"J. Clin. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e78469","DOI":"10.7554\/eLife.78469","article-title":"Trio-based whole exome sequencing in patients with suspected sporadic inborn errors of immunity: A retrospective cohort study","volume":"11","author":"Hebert","year":"2022","journal-title":"eLife"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"101761","DOI":"10.1016\/j.smim.2023.101761","article-title":"Somatic mosaicism in inborn errors of immunity: Current knowledge, challenges, and future perspectives","volume":"67","author":"Aluri","year":"2023","journal-title":"Semin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.jaci.2024.11.038","article-title":"Somatic mosaicism in genetic errors of immunity","volume":"155","author":"Cooper","year":"2025","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.it.2023.09.005","article-title":"Interplay between epigenetic and genetic alterations in inborn errors of immunity","volume":"44","author":"Calvillo","year":"2023","journal-title":"Trends Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1038\/s41586-024-08346-4","article-title":"Monoallelic expression can govern penetrance of inborn errors of immunity","volume":"637","author":"Stewart","year":"2025","journal-title":"Nature"},{"key":"ref_57","unstructured":"(2026, January 17). 6 Warning Signs for PID in Adults\u2014ESID [Internet]. Available online: https:\/\/esid.org\/updated-and-published-ebmt-esid-guidelines-for-haematopoietic-stem-cell-transplantation-for-pi\/."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"106100","DOI":"10.1016\/j.rmed.2020.106100","article-title":"How to investigate a suspected immune deficiency in adults","volume":"171","author":"Grammatikos","year":"2020","journal-title":"Respir. Med."},{"key":"ref_59","unstructured":"Sullivan, K.E., and Stiehm, E.R. (2020). Chapter 4\u2014Laboratory evaluation of primary immunodeficiency disorders. Stiehm\u2019s Immune Deficiencies, Academic Press. [2nd ed.]. Available online: https:\/\/www.sciencedirect.com\/science\/article\/pii\/B9780128167687000041."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Serban, C.L., Mihailescu, A., Miclea, D., Zimbru, C.G., Stoica, F., and Chirita-Emandi, A. (2025). Case Report: A neurodevelopmental disorder with global developmental delay, microcephaly, eye anomalies, sweat dysregulation, and skeletal implications due to an ultra-rare de novo 5q14.3q15 copy number gain. Front. Genet., 16.","DOI":"10.3389\/fgene.2025.1549685"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Serafim, V., Chirita-Emandi, A., Andreescu, N., Tiugan, D.A., Tutac, P., Paul, C., Velea, I., Mihailescu, A., \u0218erban, C.L., and Zimbru, C.G. (2019). Single Nucleotide Polymorphisms in PEMT and MTHFR Genes are Associated with Omega 3 and 6 Fatty Acid Levels in the Red Blood Cells of Children with Obesity. Nutrients, 11.","DOI":"10.3390\/nu11112600"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Pantea, C.L., Bataneant, M., Zimbru, C.G., Serban, M., Puiu, M., and Chirita-Emandi, A. (2026). Phenotypic Variability Associated with Jagunal Homolog 1 (JAGN1) Deficiency Caused by the c.63G>T Variant. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27041735"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41598-019-57080-9","article-title":"Challenges in reporting pathogenic\/potentially pathogenic variants in 94 cancer predisposing genes\u2014In pediatric patients screened with NGS panels","volume":"10","author":"Andreescu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3415\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T12:03:24Z","timestamp":1775822604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3415"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":64,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083415"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083415","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]}}}