Immune Reconstitution Inflammatory Syndrome After Hematopoietic Stem Cell Transplantation in a FOXN1 -deficient Patient.

The FOXN1 gene mutation is a unique disorder that causes the nude severe combined immunodeficiency phenotype. In patients with severe combined immunodeficiency, hematopoietic stem cell transplantation (HSCT) is life-saving if performed earlier. Thymic transplantation is the curative treatment for FOXN1 deficiency because the main pathology is thymic stromal changes. In this report, we describe the clinical features of a Turkish patient with a homozygous FOXN1 mutation treated with HSCT from his human leukocyte antigen-matched sibling. On follow-up, he showed Bacille Calmette Guerin adenitis and was evaluated as having immune reconstitution inflammatory syndrome. By presenting our patient, we aimed to draw attention to the development of HSCT and subsequent immune reconstitution inflammatory syndrome as a treatment option in patients with FOXN1 deficiency.

Comparison of mitogen-induced proliferation in child and adult healthy groups by flow cytometry revealed similarities.

The proliferation of antigen-specific lymphocyte clones, the initial step in acquired immunity, is vital for effector functions. Proliferation tests both in immunology research and diagnosis are gaining attendance gradually, while the use of adult healthy individuals as controls of pediatric patients is a question. This study aimed to investigate and compare mitogen-stimulated proliferation responses of total lymphocytes and T- and B-lymphocyte subsets in adult and children healthy donors. Nineteen children and 20 adult healthy donors were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) purified from peripheral blood samples of the donors, by Ficoll gradient centrifugation, were stained with CFSE and were cultured in a 37 â„ƒ CO2 incubator for 120 h with the absence or existence of polyclonal activators: PHA and CD-Mix. After cell culture, PBMCs were stained with monoclonal antibodies against CD4 and CD19, and proliferation percentages of CD4+ T and CD19+ B cells, together with total lymphocytes were determined by flow cytometry. This study revealed similarities between children and adult age groups, concerning mitogenic stimulation of the lymphocytes. The only difference was a significantly high proliferation of pediatric CD4+ T cells in response to PHA. CD4+ T cell responses against PHA were inversely correlated with altering age. When pediatric individuals were distributed into age groups of 0-2 years, 3-5 years, and 6-18 years, PHA responses of CD4+ cells were found to be diminished with advancing age. These findings propose the possibility of enrollment of adult healthy individuals as controls for pediatric patients.

Impaired IL-23-dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency.

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/ß (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.

Clinical, Genetic, and Outcome Characteristics of Pediatric Patients with Primary Hemophagocytic Lymphohistiocytosis.

OBJECTIVE: In this study, we sought to describe the clinical, laboratory, and genetic character- istics of patients diagnosed with primary hemophagocytic lymphohistiocytosis. Thus, we aimed to evaluate the early diagnosis and appropriate treatment options for pediatric hemophago- cytic lymphohistiocytosis patients. MATERIALS AND METHODS: Medical records of 9 patients diagnosed with primary hemophago- cytic lymphohistiocytosis between November 2013 and December 2019 were analyzed retro- spectively. Clinical, genetic, and laboratory characteristics, family histories, initial complaints, physical examination findings, age at diagnosis, treatment choices, and clinical follow-up of all patients were investigated. RESULTS: The mean age at diagnosis was 11 months (range: 1.5 months to 17 years). Genetic analysis was performed in all patients, and a disease-related mutation was detected in 8 (89%) of them. Among clinical features, 6 (66%) patients had fever, 5 (56%) had splenomegaly, 4 (44%) had lymphadenopathy, 4 (44%) had skin rash, and 4 (44%) had neurological findings. Hemophagocytosis was observed in the bone marrow samples of 6 (66%) patients. Disease remission was achieved in 7 (78%) patients. Hematopoietic stem cell transplantation was per- formed in 7 (78%) patients. CONCLUSION: Hemophagocytic lymphohistiocytosis may present with different clinical symptoms that can cause a significant diagnostic delay. The only curative treatment option in primary hemophagocytic lymphohistiocytosis patients is hematopoietic stem cell transplantation. The chemotherapy should be started as early as possible, in order to achieve a disease remission. Patients should be referred to the appropriate bone marrow transplant center for hematopoi- etic stem cell transplantation as soon as they reach the disease remission.

Diagnosis of primary immunodeficiency diseases in pediatric patients hospitalized for recurrent, severe, or unusual infections.

BACKGROUND: Primary immunodeficiency diseases (PID) usually presents itself with recurrent, severe, and unusual infections, along with autoimmunity and various other malignancies. But, the diversity of PID often makes the diagnosis of patients difficult for physicians other than clinical immunologists. This study aimed to describe the characteristics of patients diagnosed with PIDs during the inpatient treatment for infectious diseases, and to highlight the cases in which a PID diagnosis should be considered. METHODS: The clinical, immunological, and molecular features of 81 pediatric patients treated for infectious diseases, who were diagnosed with a PID during hospitalization was retrospectively analyzed. The diagnosis was based on the PID criteria of the International Union of Immunological Societies. RESULTS: The five main PID sub-types were identified. Predominantly, antibody deficiencies were the most common (61.7%) group. The average delay in diagnosis was 34.6 months, and the positive family history rate was 24.7%, while the consanguineous marriage rate was 45.7%. Around thirty-five (43%) patients were found to have mutated PID-related genes. While lower respiratory tract infections were the most common symptom, a fever of unknown origin was another remarkable diagnosis. Eight (9.9%) patients underwent allogeneic hematopoietic stem cell transplantation. CONCLUSIONS: Clinicians should consider a PID diagnosis, especially in the cases of recurrent, severe, or atypical infections. Increased knowledge of the alarm features of PID can promote early diagnosis.

Chronic Neutropenia in Childhood: Laboratory and Clinical Features.

OBJECTIVES: To describe the clinical characteristics of patients with chronic neutropenia. METHODS: Data of 36 patients with chronic neutropenia, who were followed up in the authors' clinic between May 2013 and May 2020, were analyzed retrospectively. Patients were diagnosed based on their clinical and laboratory characteristics. RESULTS: A total of 36 patients (23 females, 13 males) were included in the study. The mean age at diagnosis was 9.85 ± 9.17 mo while the mean follow-up time was 21.83 ± 20.03 mo. The mean absolute neutrophil count (ANC) at admission was 462.5 ± 388.8 cells/mm3 (median = 375 cells/mm3), and the lowest and highest ANC mean was 241.2 ± 262.1 cells/mm3 (median = 125 cells/mm3), and 1362.9 ± 1127.9 cells/mm3 (median = 925 cells/mm3), respectively. Idiopathic neutropenia was found in 28 (77.8%) patients, autoimmune neutropenia in 6 (16.7%) patients, and congenital neutropenia in 2 (5.6%) patients. Neutrophil normalization was observed in 19 (52.8%) of the patients. CONCLUSIONS: Chronic neutropenia is a heterogeneous picture that presents with different clinical symptoms in childhood. The cause of neutropoenia in children is usually benign and resolves spontaneously but especially in those with severe neutropoenia genetic examination should be performed.

HLA - matched related donor hematopoietic stem cell transplantation in a patient with polynucleotide kinase 3-phosphatase mutation developed acute myeloid leukemia.

BACKGROUND: PNPK gene mutations result in DNA repair disorders and have a spectrum of neurodevelopmental manifestations. To date, cancer predisposition has not been described in patients with PNKP mutations. OBSERVATION: Here, we report a patient with PNKP mutation, who developed AML at age of five and underwent reduced-intensity HSCT. CONCLUSION: Although many DNA repair disorders are known to have increased risk of malignancy, association between PNKP mutations and malignancy is not well-described. This report is the first description of a PNPK mutation patient developing a malignancy and undergoing curative HSCT.

Primary antibody deficiencies in Turkey: molecular and clinical aspects.

Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n = 4), CD40L (n = 1), ICOS (n = 1), IGHM (n = 1), and TCF3 (n = 1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2-10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.

Evolution and long-term outcomes of combined immunodeficiency due to CARMIL2 deficiency.

BACKGROUND: Biallelic loss-of-function mutations in CARMIL2 cause combined immunodeficiency associated with dermatitis, inflammatory bowel disease (IBD), and EBV-related smooth muscle tumors. Clinical and immunological characterizations of the disease with long-term follow-up and treatment options have not been previously reported in large cohorts. We sought to determine the clinical and immunological features of CARMIL2 deficiency and long-term efficacy of treatment in controlling different disease manifestations. METHODS: The presenting phenotypes, long-term outcomes, and treatment responses were evaluated prospectively in 15 CARMIL2-deficient patients, including 13 novel cases. Lymphocyte subpopulations, protein expression, regulatory T (Treg), and circulating T follicular helper (cTFH ) cells were analyzed. Three-dimensional (3D) migration assay was performed to determine T-cell shape. RESULTS: Mean age at disease onset was 38 ± 23 months. Main clinical features were skin manifestations (n = 14, 93%), failure to thrive (n = 10, 67%), recurrent infections (n = 10, 67%), allergic symptoms (n = 8, 53%), chronic diarrhea (n = 4, 27%), and EBV-related leiomyoma (n = 2, 13%). Skin manifestations ranged from atopic and seborrheic dermatitis to psoriasiform rash. Patients had reduced proportions of memory CD4+ T cells, Treg, and cTFH cells. Memory B and NK cells were also decreased. CARMIL2-deficient T cells exhibited reduced T-cell proliferation and cytokine production following CD28 co-stimulation and normal morphology when migrating in a high-density 3D collagen gel matrix. IBD was the most severe clinical manifestation, leading to growth retardation, requiring multiple interventional treatments. All patients were alive with a median follow-up of 10.8 years (range: 3-17 years). CONCLUSION: This cohort provides clinical and immunological features and long-term follow-up of different manifestations of CARMIL2 deficiency.

Clinical Efficacy of Ruxolitinib Monotherapy and Haploidentical Hematopoeitic Stem Cell Transplantation in a Child with Philadelphia Chromosome-like Relapsed/Refractory acute lymphoblastic leukemia.

INTRODUCTION: (Ph-like) ALL is a subset of leukemia which has a gene expression profile similar to Ph+disease, but without the presence of BCR-ABL1 translocation. CASE DESCRIPTION: We reported an exceptional case of a child with relapsed Ph-like ALL with IKZF1 gene deletion treated with high-dose ruxolitinib as monotherapy, after multi-agent chemotherapy. He remains in continued MRD-negative leukemia remission with full donor chimerism at 12 months post-HSCT. DISCUSSION: The circumstance that makes our case featured is the usage of ruxolitinib as monotherapy. This report, we believe, is a pioneering report for a frequent disease with a high risk of failure for the outcome.

Eltrombopag for treatment of thrombocytopenia after allogeneic hematopoietic cell transplantation in children: Single-centre experience.

Delayed recovery of thrombocytopenia is a well-known complication after allogeneic HSCT. Eltrombopag (ELT), a thrombopoietin receptor agonist (TRAs), induces platelet maturation and release. Mostly conducted in adults, some of the previous studies have shown that ELT seems to enhance platelet recovery for post-allogeneic HSCT thrombocytopenia, appears efficacious, and offers transfusion independence. To evaluate the safety and efficacy of ELT in pediatric patients with prolonged isolated thrombocytopenia (PIT) or secondary failure of platelet recovery (SFPR) after alloHSCT. Retrospective analysis of childhood patients who received treatment with ELT for persistent thrombocytopenia after alloHSCT between May 2016 and August 2019. We evaluated the safety and efficacy of ELT in 18 childhood patients with PIT or SFPR after alloHSCT. Eltrombopag (50 mg/d) treatment was started in all patients, above 6 years of age and 20 kg weight, who had thrombocytopenia despite neutrophil engraftment on the 30th day of HSCT. Our objective was to decrease the need for platelet transfusion and have a platelet count of more than 50 000/µL. The overall response rate was 77.7%. The median time to achieve a platelet level above 30 000/µL and 50 000/µL was 21 and 44 days, respectively. In four patients, platelet count never reached 30 000/mm3 . In two patients, the treatment was discontinued due to grade 3 hepatotoxicity. Our study supports the efficacy and relative safety of ELT use for the treatment of PIT and SFPR seen after alloHSCT in children.

Decreased frequency of allergy in juvenile idiopathic arthritis: Results of a case-control study.

OBJECTIVES: To determine the frequency of Th2-mediated allergic diseases (AD) in mainly Th1-driven juvenile idiopathic arthritis (JIA) subtypes. METHODS: Ninety-nine JIA patients and 128 control subjects were enrolled in a prospective case-control study. All subjects were assessed with standard allergy questionnaire, complete blood cell count, and total serum immunoglobulin (sIg) E. sIgs G, A, M, Juvenile Arthritis Disease Activity Score-27 (JADAS27), and serum acute phase reactants (sAPR) were obtained in JIA. In the presence of allergic symptoms, skin prick (SPT) and pulmonary function tests (PFT) were performed. RESULTS: Despite similar allergy risk factors, the frequencies of asthma and allergic rhinitis were lower in JIA group (all p ≤ .02). Allergic patients with JIA performed lower FEV1/FVC ratio, PEF, and FEF25-75 compared to the control group (all p ≤ .04). JADAS27 and sAPR were similar among JIA patients with and without AD. Two JIA patients were found to have hypogammaglobulinemia. CONCLUSION: The frequencies of AD, asthma, and allergic rhinitis may decrease in Th1-mediated JIA subtypes although the coexistence does not appear to affect the severity of arthritis whereas allergic symptoms may resolve after immunosuppressive treatment. PFTs should be obtained periodically in JIA. JIA patients may have an underlying primary immunodeficiency (ID) or immunosuppressive drugs may cause secondary ID.KEY POINTSCompared to the population, the frequency of Th2-mediated allergic diseases is lower in oligoarthritis and RF-negative polyarthritis that are primarily driven by a Th1 activity.The coexistence of allergic diseases in juvenile idiopathic arthritis does not affect the severity of arthritis.Pulmonary function tests can be thought to be obtained periodically in juvenile idiopathic arthritis.Immunological workup should be considered in atypically or severely presented patients with juvenile idiopathic arthritis before the initiation of immunosuppressive therapy to differentiate primary and secondary immunodeficiency.

Genetic Characteristics, Infectious, and Noninfectious Manifestations of 32 Patients with Chronic Granulomatous Disease.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare genetic disorder characterized by failure of phagocytic leukocytes to destroy certain microbes. We present a study on CGD patients enrolled at a single medical center concerning the infectious and noninfectious complications and genetic properties of the disease. METHODS: Icotinamide adenine dinucleotide phosphate oxidase activity and the expression of flavocytochrome b558 were measured by flow cytometry, and clinical outcomes of the patients were listed in relation to the genetic results. RESULTS: The clinical and genetic findings of 32 pediatric cases with CGD from 23 families were enrolled. Pneumonia and anemia were the most common infectious and noninfectious symptoms. Genetic analysis showed that 10 families (43.5%) carried CYBB variants and 13 families (56.5%) have autosomal recessive (AR) CGD, in which 6 families (26%) carried NCF1 variants, 4 (17.4%) carried CYBA variants, and 3 (13%) carried NCF2 variants. The median age of clinical onset was 3.3 and 48 months for patients with X-linked CGD (X-CGD) and AR-CGD, respectively. The onset of symptoms before age 1 year was 94% in X-CGD, 28.5% in AR-CGD, and 12.5% in patients with oxidase residual activity. Moreover, a de novo germline mutation at c.1415delG in CYBB (OMIM#300481) and a novel c.251_263del13bp in CYBA (OMIM#608508) were also investigated. CONCLUSIONS: Ihydrorhodamine-1,2,3 assay could not detect carrier mother in de novo case with CYBB variant. Most X-CGD patients have the onset of symptoms before age 1 year. Additionally, residual oxidase activity in AR-CGD causes a delay in onset, diagnosis, and prophylaxis. The protective role of residual activity is limited while the infection is ongoing and becoming serious.

Mutational landscape of severe combined immunodeficiency patients from Turkey.

Severe 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.

Clinical and immunophenotypic characteristics of patients with chromosome 22q11.2 deletion syndrome: a single institution's experience.

AIM: The aim of this study was to identify the clinical and immunologic features of patients with 22q11.2 deletion syndrome who were followed up in our clinic. Thus, it is aimed to identify the syndrome early, choose the right treatment options according to humoral and cellular immunologic analysis, and enlighten how to follow up these kinds of patients with immunodeficiencies. MATERIAL AND METHODS: We retrospectively collected data by reviewing the files of 11 patients with 22q11.2 deletion syndrome who were followed up in our clinic between January 2003 and January 2015. The diagnoses were based on the patients' clinical, genetic, and immunologic features. Demographic features, family history, initial symptoms on admission, physical findings, and results of immunologic studies of the patients. Age of diagnosis, treatment options, and clinical follow-up were evaluated. RESULTS: The patients' diagnosis age ranged from 1-11 months and the most common symptoms of admission were cardiac murmur and atypical facial appearance, which were detected during a routine physical examination. All patients had cardiac anomalies, and four patients had a history of cardiovascular surgery. Eight patients (72.7%) had a history of severe infection; recurrent lower respiratory tract infections were reported in six patients (54.5%), pulmonary tuberculosis in one patient (9.1%), and moniliasis resistant to treatment was detected in one patient. None of the patients required intravenous immunoglobulin replacement therapy, and antibiotic prophylaxis was administered to two patients with lymphopenia. CONCLUSION: 22q11.2 deletion syndrome is a multi-systemic disorder that should be evaluated by a multidisciplinary team. It should be kept in mind for patients with neonatal hypocalcemic tetany or recurrent infections or atypical facial appearance with cardiac anomalies. Early diagnosis should lead to immunologic analysis and enable the choice of treatment. Preventive measures against infection is recommended for the patients with incomplete immunodeficiency, and thymus transplantation is recommended for patients with complete immunodeficiency.

AMAÇ: Bu çalismada klinigimizde 22q11.2 delesyon sendromu tanisi ile izlenmekte olan hastalarin klinik ve immünolojik niteliklerinin tanimlanmasi amaçlanmistir. Böylece hastaligin erken taninmasina yardimci olmak, humoral ve hücresel immünolojik verilere göre tedavi seçeneklerine yönlendirmek ve bu immün yetersizlik hastalarinin nasil izlenecegine isik tutmak hedeflenmistir. GEREÇ VE YÖNTEMLER: Klinigimizde, Ocak 2003-Ocak 2015 tarihleri arasinda 22q11.2 delesyon sendromu tanisi ile izlenmekte olan 11 olgunun dosya verileri geriye dönük olarak incelendi. Hastalarin tanisi; klinik, genetik ve immünolojik niteliklere göre konuldu. Çalismaya alinan tüm hastalarin demografik nitelikleri, aile öyküsü, basvuru yakinmalari, fizik baki bulgulari, immünolojik inceleme sonuçlari, tani yasi, tedavi seçenegi ile klinik izlemleri irdelendi. BULGULAR: Hastalarin tani yasi 1-11 ay arasinda degismekte olup, en sik basvuru yakinmasi fizik baki sirasinda farkedilen atipik yüz görünümü ve kalpte duyulan üfürüm idi. Tüm hastalarin kalbinde anomali bulunur iken, dört hastada kardiyovasküler cerrahi girisim öyküsü vardi. Sekiz hastada (%72,7) ciddi enfeksiyon geçirme öyküsü olup; alti hastada (%54,5) sik tekrarlayan alt solunum yolu enfeksiyonu, bir hastada (%9,1) akciger tüberkülozu ve bir hastada (%9,1) inatçi moniliazis saptandi. Lenfopenik olan iki hastaya (%18,2) antibiyotik profilaksisi uygulanirken, hiçbir hastada intravenöz immünglobulin replasman tedavisi gereksinimi olmadi. ÇIKARIMLAR: Kromozom 22q11.2 delesyon sendromu, çoklu organ tutulumu nedeniyle birçok uzmanlik daliyla birlikte izlenmelidir. Yenidogan döneminde hipokalsemik tetani geçiren, kalp anomalisine eslik eden atipik yüz görünümü olan ve yineleyen enfeksiyon öyküsü olan hastalarda mutlaka akla getirilmelidir. Erken tani ile hastalarin immün sistem incelemesinin yapilmasi; kismi eksiklik durumunda enfeksiyonlardan koruyucu önlemler alinmasini, tam hücresel immün bozukluk olmasi durumunda ise timus nakli yapilmasina olanak saglayacaktir.

A novel pathogenic frameshift variant of CD3E gene in two T-B+ NK+ SCID patients from Turkey.

Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency, which is characterized by the dysfunction and/or absence of T lymphocytes. Early diagnosis of SCID is crucial for overall survival, and if it remains untreated, SCID is often fatal. Next-generation sequencing (NGS) has become a rapid, high-throughput technology, and has already been proven to be beneficial in medical diagnostics. In this study, a targeted NGS panel was developed to identify the genetic variations of SCID by using SmartChip-TE technology, and a novel pathogenic frameshift variant was found in the CD3E gene. Sanger sequencing has confirmed the segregation of the variant among patients. We found a novel deletion in the CD3E gene (NM000733.3:p.L58Hfs*9) in two T-B+ NK+ patients. The variant was not found in the databases of dbSNP, ExAC, and 1000G. One sibling in family I was homozygous and the rest of the family members were heterozygous for this variant. T cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) analyses were performed for T and B cell maturation. TRECs were not detected in both patients and the KREC copy numbers were similar to the other family members. In addition, heterozygous family members showed decreased TREC levels when compared with the wild-type sibling, indicating that carrying this variant in one allele does not cause immunodeficiency, but does effect T cell proliferation. Here, we report a novel pathogenic frameshift variant in CD3E gene by using targeted NGS panel.