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Background: Inborn errors of immunity (IEI) are a group of heterogeneous disorders with geographic and ethnic diversities. Although IEI are common in Egypt, genetic diagnosis is limited due to financial restrictions. This study aims to characterize the genetic spectrum of IEI patients in Egypt and highlights the adaptation of the molecular diagnostic methods to a resource-limited setting. Methods: Genetic material from 504 patients was studied, and proper diagnosis was achieved in 282 patients from 246 families. Mutational analysis was done by Sanger sequencing, next-generation sequencing (NGS) targeting customized genes panels, and whole-exome sequencing (WES) according to the patients' phenotypes and availability of genetic testing. Results: A total of 194 variants involving 72 different genes were detected with RAG1/2 genes being the most encountered followed by DOCK8, CYBA, LRBA, NCF1, and JAK3. Autosomal recessive (AR) inheritance was detected in 233/282 patients (82.6%), X-linked (XL) recessive inheritance in 32/282 patients (11.3%), and autosomal dominant (AD) inheritance in 18/282 patients (6.4%), reflecting the impact of consanguineous marriages on the prevalence of different modes of inheritance and the distribution of the various IEI disorders. Conclusion: The study showed that a combination of Sanger sequencing in selected patients associated with targeted NGS or WES in other patients is an effective diagnostic strategy for IEI diagnosis in countries with limited diagnostic resources. Molecular testing can be used to validate other nonexpensive laboratory techniques that help to reach definitive diagnosis and help in genetic counseling and taking proper therapeutic decisions including stem cell transplantation or gene therapy. [ABSTRACT FROM AUTHOR]

Background: Egypt has a high prevalence of hepatitis C virus (HCV) infection. Limitations of the current HCV treatment in children are low rate of sustained virological response, significant side effects and high expenses, making prediction of treatment response crucial. Aim: This study aimed to investigate association of single nucleotide polymorphisms (SNPs) in interleukins (IL) 10 , 28 and 29 genes in predicting the response to therapy in HCV infected children. Methods: Sixty-six Egyptian children infected with HCV genotype 4, receiving pegylated interferon alpha 2b and ribavirin, were included. Genotyping of six SNPs in interleukin 10 , 28B and 29 gene as well as HCV genotype were analyzed by real-time polymerase chain reaction. Results: The CC genotype in IL28B; rs12979860 had 8.547 folds higher chance to develop sustained virological response than CT and TT genotypes ( P = 0.014). Genotype distribution of rs8099917 in IL28B gene ( TG and GG genotypes) was found to be 3.348 more likely not to respond to treatment than the TT genotype ( P = 0.018). In multivariate analysis, interleukin 28 gene single nucleotide polymorphisms rs 12979860 , interleukin 10 single nucleotide polymorphisms − 592A > C and basal viral load were independent variables that significantly improved prediction of response to HCV therapy. Conclusion: This association can be translated into clinical decision making for HCV treatment. [ABSTRACT FROM AUTHOR]

The present study aimed at evaluating the role of IL-1β −511 promoter and IL-1β +3953 exon 5 gene polymorphisms in the risk of developing rheumatoid arthritis (RA) and its correlation to disease activity in Egyptian patients. Thirty-two patients having RA as defined by American College of Rheumatology and 20 healthy control subjects were included. All were subjected to DNA analysis for IL-1β −511and IL-1β +3953 gene polymorphisms using PCR-RFLP technique with restriction enzymes AvaI and TaqI, respectively. No special pattern of association could be detected either between IL-1β −511 and +3953 gene polymorphisms and disease susceptibility or between the polymorphisms and the disease activity parameters represented by disease activity score 28 (DAS 28), ESR, and number of swollen and tender joints. Allele distribution failed as well to detect any association with either disease susceptibility or activity; however, a trend towards positive association involving IL-1β −511 C allele was observed ( P = 0.054). Our results suggest that IL-1β −511 and IL-1β +3953 gene polymorphisms do not influence the susceptibility to acquire RA in our population with no relation to disease activity. The complex role of the genetic factors in RA and the magnitude of the effects will require further thorough confirmations in other populations and on larger samples to acknowledge this issue. [ABSTRACT FROM AUTHOR]

Cernunnos deficiency is a rare genetic disorder characterized by immunodeficiency, microcephaly, growth retardation, bird-like facies, sensitivity to ionizing radiation, few autoimmune manifestations, premature aging of hematopoietic stem cells at an early age, and occasional myeloproliferative disease. Herein we present five Egyptian Cernunnos patients from 3 different families. We describe the patients' clinical phenotypes, their immunological profile as well as genetic results. Sequence analysis revealed three different mutations in the NHEJ1 gene: a nonsense variant c.532C > T; p.(Arg178Ter), an intronic variant c.178-1G > A and a frameshift insertion variant c.233dup; p.(Asn78LysfsTer14). In conclusion, Cernunnos deficiency can have a wide range of clinical features. The characteristic immune profile including a decrease in recent thymic emigrants and naive T cells, markedly elevated memory T cells together with normal to high IgM, and a decrease in IgG and IgA. This immune profile is highly suggestive of Cernunnos deficiency in T-B-NK + SCID patients especially surviving for older ages. • This is the first Egyptian report of patients with mutations in NHEJ1 gene. • c.532C > T; p.(Arg178Ter), c.178-1G > A and c.233dup had been identified in NHEJ1 gene. • Cernunnos deficiency can have a wide range of clinical features. • Suspicion is raised in SCID with elevated memory and decrease naïve T cells. • Presence of BM aplasia and absence of malignancies are disease hallmarks. [ABSTRACT FROM AUTHOR]