Fırtına, SinemNg, Yuk YinNg, Özden HatırnazKıykım, AyçaAydiner, ElifNepesov, SerdarCamcıoğlu, YıldızSayar, Esra H.Reisli, IsmailTorun, Selda H.Çöğürlü, TubaUygun, DilaraŞimşek, Işıl E.Kaya, AyşenurÇipe, FundaÇağdaş, DenizYücel, EsraUygun, VedatBarış, SafaÖzen, AhmetÖzbek, UğurSayitoğlu, Müge2024-02-232024-02-232020-06-02Fırtına, S. vd. (2020). "Mutational landscape of severe combined immunodeficiency patients from Turkey". International Journal of Immunogenetics, 47(6), 529-538.1744-31211744-313Xhttps://onlinelibrary.wiley.com/doi/10.1111/iji.12496https://hdl.handle.net/11452/39930Severe combined immunodeficiency (SCID) has a diverse genetic aetiology, where a clinical phenotype, caused by single and/or multiple gene variants, can give rise to multiple presentations. The advent of next-generation sequencing (NGS) has recently enabled rapid identification of the molecular aetiology of SCID, which is crucial for prognosis and treatment strategies. We sought to identify the genetic aetiology of various phenotypes of SCIDs and assessed both clinical and immunologic characteristics associated with gene variants. An amplicon-based targeted NGS panel, which contained 18 most common SCID-related genes, was contumely made to screen the patients (n = 38) with typical SCID, atypical SCID or OMENN syndrome. Allelic segregations were confirmed for the detected gene variants within the families. In total, 24 disease-causing variants (17 known and 7 novel) were identified in 23 patients in 9 different SCID genes: RAG1 (n = 5), RAG2 (n = 2), ADA (n = 3), DCLRE1C (n = 2), NHEJ1 (n = 2), CD3E (n = 2), IL2RG (n = 3), JAK3 (n = 4) and IL7R (n = 1). The overall success rate of our custom-made NGS panel was 60% (39.3% for NK+ SCID and 100% for NK- SCID). Incidence of autosomal-recessive inherited genes is more frequently found in our cohort than the previously reported populations probably due to the high consanguineous marriages in Turkey. In conclusion, the custom-made sequencing panel was able to identify and confirm the previously known and novel disease-causing variants with high accuracy.eninfo:eu-repo/semantics/closedAccessPrimary immunodeficiencySCIDTargeted next-generation sequencingDCLRE1C artemis mutationsGeneVariantsDiseasesGenetics & heredityImmunologyAdenosine deaminaseAdolescentAdultAllelesB-LymphocytesCD3 complexChild, preschoolDNA mutational AnalysisDNA repair enzymesDNA-binding proteinsEndonucleasesFemaleGenetic variationHigh-throughput nucleotide sequencingHomeodomain proteinsHumansInfantInfantNewbornInterleukin receptor common gamma subunitsInterleukin-7 receptor alpha subunitJanus kinase 3Killer cells, naturalMaleMutationNuclear proteinsPhenotypePrognosisSevere combined immunodeficiencyT-lymphocytesTurkeyArticle0005347410000012-s2.0-8508557085452953847632445296https://doi.org/10.1111/iji.12496Genetics & heredityImmunologySevere Combined Immunodeficiency; Newborn Screening; ImmunosuppressionAntigenCD3E antigenGenomic DNAInterleukin 2 receptor gammaInterleukin 7 receptorJanus kinase 3RAG1 proteinRAG2 proteinUnclassified drugADA protein, humanAdenosine deaminaseCD3 antigenCD3E protein, humanDCLRE1C protein, humanDNA binding proteinDNA ligaseEndonucleaseHomeodomain proteinIL2RG protein, humanIL7R protein, humanInterleukin 2 receptor gammaInterleukin 7 receptor alphaJAK3 protein, humanJanus kinase 3NHEJ1 protein, humanNuclear proteinRAG-1 proteinRAG2 proteinHuman3' untranslated region5' untranslated regionAdultAnemiaAutosomal recessive disorderB lymphocyteBronchiectasisCandidiasisCD3+ T lymphocyteCD4+ T lymphocyteChildClinical articleClinical featureConjunctivitisControlled studyCORO1A geneDCLRE1C geneFemaleGeneGene identificationGenetic variationGenotype phenotype correlationGrowth retardationHigh throughput sequencingHumanInfantLIG4 geneLymphocytopeniaMalabsorptionMaleMutationNatural killer cellOmenn syndromeOtitis mediaPhenotypePneumoniaPreschool childPriority journalSchool childSevere combined immunodeficiencyTurkey (republic)Upper respiratory tract infectionZBTB24 geneAdolescentAlleleDna mutational analysisEpidemiologyGeneticsHigh throughput sequencingImmunologyMutationNewbornPrognosisSevere combined immunodeficiencyT lymphocyteTurkey (bird)