1.Analysis of clinical phenotype and variant of RAG1 gene in a child with B-cell-negative Severe Combined Immunodeficiency.
Juan HUANG ; Xiaofeng GUO ; Wei JI
Chinese Journal of Medical Genetics 2023;40(2):238-241
OBJECTIVE:
To report on a child with B-cell-negative severe combined immunodeficiency (B-SCID) manifesting as fulminant myocarditis and carry out genetic testing for her.
METHODS:
A child with B-SCID who presented at Fujian Maternity and Child Health Care Hospital on January 31, 2021 was selected as the subject. Whole exome sequencing was carried out for her. Candidate variant was verified by Sanger sequencing.
RESULTS:
The female infant had developed recurrent skin and lung infections soon after birth, and was admitted due to fulminant myocarditis. Serological examination has disclosed a remarkable reduction in immunoglobulins. Flow cytometric analysis revealed that her peripheral blood T and B lymphocytes and NK cells were significantly reduced. Whole exome sequencing revealed that she has harbored a homozygous c.C3007T (p.Q1003X) nonsense variant of the RAG1 gene, for which both of her parents were heterozygous carriers. The variant has not been recorded in normal population databases. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic.
CONCLUSION
A case of RAG1 gene associated B-SCID has been diagnosed. Above finding has enriched the spectrum of RAG1 gene variants and enabled early diagnosis and intervention of the disease.
Female
;
Humans
;
Pregnancy
;
Genetic Testing
;
Homeodomain Proteins/genetics*
;
Mutation
;
Myocarditis/genetics*
;
Phenotype
;
Severe Combined Immunodeficiency/diagnosis*
;
Infant
2.Pneumocystis jirovecii pneumonia in pediatric patients: an analysis of 15 confirmed consecutive cases during 14 years.
Kyung Ran KIM ; Jong Min KIM ; Ji Man KANG ; Yae Jean KIM
Korean Journal of Pediatrics 2016;59(6):252-255
PURPOSE: Pneumocystis jirovecii pneumonia occurs in various immunocompromised patients. Despite the prophylaxis strategies in clinical practice, certain patients develop P. jirovecii pneumonia. This study was performed to investigate pediatric cases with P. jirovecii pneumonia in a single center. METHODS: We identified pediatric patients younger than 19 years with microbiologically confirmed P. jirovecii pneumonia from January 2000 to February 2014. A retrospective chart review was performed. RESULTS: Fifteen episodes of P. jirovecii pneumonia in 14 patients were identified with median age of 8.3 years (range, 0.4-18.6 years). Among these patients, 11 patients had hematology-oncology diseases, 2 had primary immunodeficiency disorders (one with severe combined immunodeficiency and the other with Wiskott Aldrich syndrome), 1 had systemic lupus erythematosus and 1 received kidney transplant. Four patients were transplant recipients; 1 allogeneic and 2 autologous hematopoietic cell transplant and 1 with kidney transplant. The median absolute lymphocyte count at the diagnosis of P. jirovecii pneumonia was 5,156 cells/mm³ (range, 20-5,111 cells/mm³). In 13 episodes (13 of 15, 86.7%), patients were not receiving prophylaxis at the onset of P. jirovecii pneumonia. For treatment, trimethoprim/sulfamethoxazole was given as a main therapeutic agent in all 15 episodes. Steroid was given in 9 episodes (60%). Median treatment duration was 15 days (range, 4-33 days). Overall mortality at 60 days was 35.7% (5 of 14). CONCLUSION: Majority of our patients developed P. jirovecii pneumonia while not on prophylaxis. Continuous efforts and more data are needed to identify high risk patients who may get benefit from P. jirovecii pneumonia prophylaxis.
Diagnosis
;
Humans
;
Immunocompromised Host
;
Kidney
;
Lupus Erythematosus, Systemic
;
Lymphocyte Count
;
Mortality
;
Pediatrics
;
Pneumocystis carinii
;
Pneumocystis jirovecii*
;
Pneumocystis*
;
Pneumonia*
;
Retrospective Studies
;
Severe Combined Immunodeficiency
;
Transplant Recipients
;
Transplants
3.Flow Cytometry for the Diagnosis of Primary Immunodeficiency Diseases: A Single Center Experience
Won Kyung KWON ; SooIn CHOI ; Hee jin KIM ; Hee Jae HUH ; Ji Man KANG ; Yae Jean KIM ; Keon Hee YOO ; Kangmo AHN ; Hye Kyung CHO ; Kyong Ran PECK ; Ja Hyun JANG ; Chang Seok KI ; Eun Suk KANG
Allergy, Asthma & Immunology Research 2020;12(2):292-305
PURPOSE: While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute.METHODS: Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing.RESULTS: Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring.CONCLUSIONS: The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.
Agammaglobulinemia
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Diagnosis
;
Exome
;
Flow Cytometry
;
Genetic Testing
;
Granulomatous Disease, Chronic
;
Humans
;
Immunophenotyping
;
Korea
;
Leukocytes
;
Lymphocyte Subsets
;
Lymphohistiocytosis, Hemophagocytic
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Phenotype
;
Retrospective Studies
;
Seoul
;
Severe Combined Immunodeficiency
;
Tertiary Healthcare
4.Use of Stem Cell in Fetal Therapy: Current Status and Future Perspectives.
Journal of the Korean Society of Maternal and Child Health 2017;21(2):92-99
During the past decades, there has been a great evolution in the field of fetal therapy for congenital defects. Prenatal screening or diagnostic methods including non-invasive and invasive methods and fetal ultrasound have led to earlier and more accurate diagnosis of congenital anomalies. Recent advances in several therapeutic techniques including ultrasound-guided needle therapy, laser therapy or fetal endoscopy, have allowed some fetuses at risk with anatomical defects, to be corrected in utero but still, its clinical indications remain limited. Over the last 30 years, many researchers found usefulness of pluripotent stem cells from amniotic fluid and placenta because they are sources of diverse progenitor cell populations called mesenchymal stem cells. In some human conditions like severe combined immunodeficiency syndrome and chronic granulomatous disease, fetal therapy using stem cell replacement showed some promising results in researches but more studies are required to apply in clinical settings. The aim of this article is to summarize a current status and future perspective of stem cell therapy for treatment of congenital fetal anomalies.
Amniotic Fluid
;
Congenital Abnormalities
;
Diagnosis
;
Endoscopy
;
Female
;
Fetal Therapies*
;
Fetus
;
Granulomatous Disease, Chronic
;
Humans
;
Laser Therapy
;
Mesenchymal Stromal Cells
;
Needles
;
Placenta
;
Pluripotent Stem Cells
;
Prenatal Diagnosis
;
Severe Combined Immunodeficiency
;
Stem Cells*
;
Ultrasonography
5.A Clinical Study of Primary Immunodeficiency Disease in a Single Center in Seoul from 1996 to 2004.
Jee Hyun LEE ; Woo Yun SOHN ; Hwa Young PARK ; Su Jung HWANG ; Won Hee SEO ; Su Jung KIM ; So Hyun AHN ; Eun Kyeong JO ; Kang Mo AHN ; Sang Il LEE
Pediatric Allergy and Respiratory Disease 2005;15(4):368-380
PURPOSE: Although primary immunodeficiency disorders are relatively rare, early diagnosis provides the opportunity to reduce morbidity and mortality. The aim of this study was to investigate disease distribution, clinical manifestations, genetic mutation, treatment and prognosis of primary immunodeficiency disorders of childhood. METHODS: We retrospectively reviewed the medical records of 15 cases with primary immunodeficiency disorders between 1996 and 2004 in Samsung Seoul Hospital, Seoul, Korea. RESULTS: The most common primary immunodeficiency was common variable immunodeficiency (CVID) (n=7), followed by X-linked agammaglobulinemia (XLA) (n=3), severe combined immunodeficiency (SCID) (n=2), hyper IgM syndrome (n=1), selective IgA deficiency (n=1), and chronic granulomatous disease (CGD) (n=1). Most cases had recurrent infections such as otitis media, bacterial pneumonia, sinusitis and other respiratory infections during infancy. The age at diagnosis ranged from 4 months to 17 years with a median age of 5 years. The male to female ratio was 11 to 4. Eleven patients were diagnosed with primary immunodeficiency diseases following respiratory infection, while the other 4 patients had pulmonary tuberculosis, perianal abscess, bacterial meningitis, septic arthritis. All the patients with XLA and CVID were regularly treated with IVIG. Two cases of SCID underwent successful bone marrow transplantation without complications. The patients with hyper IgM syndrome died due to severe infection even after bone marrow transplantation. CONCLUSION: Fifteen variable cases of primary immunodeficiency were diagnosed during 9 years. A high index of suspicion is required in children with recurrent or severe infections for the diagnosis of primary immunodeficiency, because early diagnosis and treatment can reduce mortality and morbidity.
Abscess
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Agammaglobulinemia
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Arthritis, Infectious
;
Bone Marrow Transplantation
;
Child
;
Common Variable Immunodeficiency
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Diagnosis
;
Early Diagnosis
;
Female
;
Granulomatous Disease, Chronic
;
Hospital Distribution Systems
;
Humans
;
Hyper-IgM Immunodeficiency Syndrome
;
IgA Deficiency
;
Immunoglobulins, Intravenous
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Korea
;
Male
;
Medical Records
;
Meningitis, Bacterial
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Mortality
;
Otitis Media
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Pneumonia, Bacterial
;
Prognosis
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Respiratory Tract Infections
;
Retrospective Studies
;
Seoul*
;
Severe Combined Immunodeficiency
;
Sinusitis
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Tuberculosis, Pulmonary
6.Overview of clinical occurrence of primary immunodeficiency disorders in children.
Hui-jun ZHAO ; Tong-xin CHEN ; Yi-qun HAO ; Yun-fang ZHOU ; Da-ming YING
Chinese Journal of Pediatrics 2006;44(6):403-406
OBJECTIVEMore than one hundred primary immunodeficiency disorders have been discovered so far. But the incidence of these disorders in our country is still not clear, so we analyzed the clinical data of 93 children with primary immunodeficiency disorders seen in our hospital in recent 30 years to understand the occurrence of primary immunodeficiency disorders in children, to promote the clinicians to become familiar with these disorders, to improve the nationwide registry system and to establish the basis for the treatment and prevention in future.
METHODSTo analyze the constituent ratio of the 93 children with primary immunodeficiency disorders seen in our hospital from 1974 to 2003, diagnostic and classification criteria were set by taking the proposal by International Union of Immunological Societies (IUIS) PID classification committee in 2003 into account. All the data were analyzed retrospectively.
RESULTSIn the 93 children with primary immunodeficiency disorders, antibody deficiencies were the most frequent (39.8%) finding, followed by combined immunodeficiency, combined T- and B-cell disorders (22.6%), and T lymphocytic deficiencies alone (14.0%). Immunodeficiency with other major defects accounted for 12.9%, phagocytic disorders 9.7%, and complement deficiencies 1.1%. Thus, there seemed to be a tendency that the incidence increased with time. The incidence of these disorders has increased significantly as shown by 50 diagnosed cases in children with these disorders since 1996. Sixteen children died, with the highest mortality occurred with combined immunodeficiency. Seven children developed bronchiectasis. Two children suffered from persistent diarrhea while one of the two was complicated with persistent intestinal fistula. One child developed juvenile rheumatoid arthritis, another one with granulocytopenia and iridocyclitis, and the other with allergic purpura. The boys: girls ratio for all disorders was 3:1. The age of onset ranged from 10 days to 37 years of age.
CONCLUSIONSThere are vast variety of primary immunodeficiency disorders in our area and antibody deficiency is the most common abnormality. Combined immunodeficiency has early onset age and high mortality rate. With the great improvement of the diagnostic techniques, these disorders have become a group of important disorders and all the clinicians should pay great attention to these disorders.
Adolescent ; Adult ; Agammaglobulinemia ; epidemiology ; immunology ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Hospitals ; Humans ; Immunologic Deficiency Syndromes ; classification ; diagnosis ; epidemiology ; immunology ; Incidence ; Infant ; Infant, Newborn ; Male ; Registries ; Retrospective Studies ; Risk Factors ; Severe Combined Immunodeficiency ; epidemiology ; immunology ; Sex Factors ; Time Factors
7.Clinical phenotype and gene diagnostic analysis of Omenn syndrome.
Yan-qiong WANG ; Yu-xia CUI ; Jie FENG
Chinese Journal of Pediatrics 2013;51(1):64-68
OBJECTIVEOmenn syndrome is a rare autosomal recessive hereditary severe combined immunodeficiency. The purpose of this study was to understand clinical characteristics and genetic mutation type of Omenn syndrome and to improve the recognition of Omenn syndrome among pediatric clinicians.
METHODOne suspected case of severe combined immunodeficiency was found to have pneumonia repeatedly, intractable diarrhea, poor antibiotic treatment effect, lymphadenopathy, hepatosplenomegaly and erythroderma. The patient was diagnosed as having Omenn syndrome by RT-PCR, and the expression of RAG1/RAG2 and gene analysis of RAG1/RAG2 were performed.
RESULTThe classification of lymphocyte was CD3(+) cells (35.3%), CD19(+) cells (0.4%), CD16(+) cells (57.6%). After stimulation with phytohemagglutinin (PHA), lymphocyte proliferation of the child was extremely low. Genetic studies showed RAG1 homozygous deletion mutation (2302 del T). He had detectable activated T-lymphocytes with low circulating B-lymphocytes and no evidence of maternal T-cell engrafment as indicated by the short tandem repeat (STR) analysis.
CONCLUSIONOmenn syndrome is a severe combined immunodeficiency disease caused by mutations in the RAG1/RAG2 gene. The disease has been reported rarely in China. The clinical manifestations of the disease is early postnatal repeated infections and erythroderma. Mutation analysis of RAG1/RAG2 gene may help to confirm the diagnosis and may be useful in early immune reconstitution and genetic counseling.
Amino Acid Sequence ; Biomarkers ; blood ; DNA Mutational Analysis ; DNA-Binding Proteins ; genetics ; Genotype ; Homeodomain Proteins ; genetics ; Humans ; Infant ; Lymphocytes ; immunology ; pathology ; Male ; Microsatellite Repeats ; Mutation ; Nuclear Proteins ; genetics ; Phenotype ; Receptors, Antigen, T-Cell, alpha-beta ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Severe Combined Immunodeficiency ; diagnosis ; genetics ; pathology
8.X-linked Severe Combined Immunodeficiency Syndrome: The First Korean Case with gamma c Chain Gene Mutation and Subsequent Genetic Counseling.
Eun Kyeong JO ; Satoru KUMAKI ; Du WEI ; Shigeru TSUCHIYA ; Hirokazu KANEGANE ; Chang Hwa SONG ; Ha Young NOH ; Young Ok KIM ; So Yeon KIM ; Hae Yul CHUNG ; Yoon Ha KIM ; Hoon KOOK
Journal of Korean Medical Science 2004;19(1):123-126
X-linked severe combined immunodeficiency (X-SCID) is a rare, life-threatening immune disorder, caused by mutations in the gamma c chain gene, which encodes an essential component of the cytokine receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. A 13-month-old boy with recurrent infections who had reduced serum immunoglobulin levels and decreased numbers of CD3, CD16/56 cells was evaluated for gamma c chain gene mutation and protein expression. The patient had a C-to-T point mutation at nucleotide position 690, one of the hot spots, resulting in a single amino acid substitution of cysteine for arginine (R226C), as determined by direct sequencing and PCR-RFLP. The patient's mother was a heterozygous carrier. Percutaneous umbilical cord blood sampling was performed at the 6-month of gestation in a subsequent pregnancy. As the immunophenotype of the fetus showed an identical pattern, the pregnancy was terminated and genetic analysis of the abortus confirmed recurrence. This is the first report of the molecular diagnosis of X-SCID in Korea. Genetic analysis of the gamma c chain gene is useful for definite diagnosis and genetic counseling for X-SCID.
Arginine/chemistry
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Cysteine/chemistry
;
DNA/metabolism
;
DNA Mutational Analysis
;
Female
;
Flow Cytometry
;
Genetic Counseling/*methods
;
Heterozygote
;
Human
;
Immunoglobulins/metabolism
;
Immunophenotyping/methods
;
Korea
;
*Linkage (Genetics)
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Male
;
*Mutation
;
Pedigree
;
Point Mutation
;
Polymerase Chain Reaction
;
Polymorphism, Restriction Fragment Length
;
Receptors, Immunologic/*genetics
;
Sequence Analysis, DNA
;
Severe Combined Immunodeficiency/*diagnosis/*genetics
;
Support, Non-U.S. Gov't
;
Time Factors
;
*X Chromosome