Humans ; Immunologic Deficiency Syndromes/genetics*

OBJECTIVE: To explore the clinical feature, diagnosis and phenotype of Majeed syndrome. METHODS: Clinical manifestation, diagnostic process, imaging feature and genetic testing of an ethnic Han Chinese patient with Majeed syndrome were reviewed. RESULTS: The patient, a 3-year-9-month-old boy, had featured psychomotor retardation and developed bone pain from 8 month on. The child had tenderness of the lower limbs and presented with repeatedly joint swelling and pain accompanied by fever. Physical signs included limb muscle weakening, slightly decreased muscle tone, reduced muscle volume and positive Gower sign. High-throughput sequencing revealed that the child has carried compound heterozygous variants of the LPIN2 gene, including c.1966A>G and c.2534delG. MRI showed multiple lesions in bilateral knee joints and distal middle tibia presenting as patchy SPAIR high signals with unclear edge, in addition with edema of soft tissue surrounding the right distal femur. CONCLUSION Majeed syndrome is characterized by chronic and recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and growth retardation. Surrounding muscle tissue of osteomyelitis may also be involved. The syndrome may also affect the central nervous system, resulting in delayed language and motor development. Discovery of multiple pathological variants of the LPIN2 gene suggested that the clinical phenotype of this syndrome may vary between patients to some extent.
Anemia, Dyserythropoietic, Congenital/genetics* ; Child ; Genetic Testing ; Humans ; Immunologic Deficiency Syndromes/genetics* ; Infant ; Male ; Osteomyelitis/genetics*

This research investigated the clinical features of immunodeficiency disease and the features of the mutation of its pathogenic genes. All 7 patients were boys aged 5 months to 4 years and 6 months and had a history of recurrent respiratory infection and pneumonia, low levels of IgM and IgG, and abnormal absolute values or percentages of lymphocyte subsets. High-throughput sequencing showed c.1684C>T mutations in the BTK gene in patient 1 and IVS8+2T>C splice site mutations in the BTK gene in patient 2. Both of these mutations came from their mothers. Patients 3, 4, and 5 had mutations in the IL2RG gene, i.e., c.298C>T, IVS3-2A>G, and c.164T>A, among which c.164T>A mutations had not been reported. Patient 6 had c.204C>G mutations in the RAG2 gene. Patient 7 had complex heterozygous mutations of c.913C>T and c.824G>A in the RAG2 gene, which came from his father and mother, respectively. Patients with immunodeficiency disease have abnormal immunological indices, and high-throughput sequencing helps to make a definite diagnosis.
Agammaglobulinaemia Tyrosine Kinase ; Agammaglobulinemia ; genetics ; Child, Preschool ; Computational Biology ; DNA-Binding Proteins ; genetics ; Genetic Diseases, X-Linked ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Immunologic Deficiency Syndromes ; genetics ; therapy ; Infant ; Interleukin Receptor Common gamma Subunit ; genetics ; Male ; Mutation ; Nuclear Proteins ; genetics ; Protein-Tyrosine Kinases ; genetics

DNA End-Joining Repair ; Humans ; Immunologic Deficiency Syndromes ; genetics

OBJECTIVESchimke immuno-osseous dysplasia (SIOD), is an autosomal recessive inherited disease caused by SMARCAL1 (MIM:20606622) mutations, while in about half of the patients no any mutation in SMARCAL1 could be found. This disease involves multiple systems and is characterized by short and dissymmetric stature with spondyloepiphyseal dysplasia, progressive renal failure, lymphopenia with recurrent infections, and hyperpigmented macules. This study aimed to analyze SMARCAL1 gene of 2 unrelated suspected SIOD children, to make definite diagnosis, and find more SMARCAL1 mutation types of Chinese SIOD.

METHODTwo suspected Chinese Han male SIOD children who visited our hospital from 2008 to 2014, aged 3 y 6 m and 7 y 8 m, both were short and had spondyloepiphyseal dysplasia, progressive renal failure, lymphopenia with recurrent infections. After informed consent, they and their parents's DNA were extracted from blood. PCRs for all 16 exons of SMARCAL1 were performed and PCR products were purified by 2% gel electrophoresis and sequenced directly. Pathogenicity of missense variations was confirmed by SIFT and sequencing SMARCAL1 of fifty normal controls.

RESULT(1) Four gene variations were found in the two children: Two reported missense mutations c.1129G>C, p.Glu377Gln and c.1933C>T, p. Arg645Cys. Two splicing mutations c.1334+1G>A and c.2142-1 G>A were detected. (2) c.1129G>C, p.Glu377Gln were reported as a disease-causing mutations before, but it was an single nucleotide polymorphism (SNP) which was found in 15 of 50 normal controls. (3) Two novel splicing mutations were found in this study: c.1334+1G>A and c.2142-1 G>A.

CONCLUSION(1) We detected 3 disease-causing mutations in 2 SIOD children by SMARCAL1 gene analysis, while 2 splicing mutations were novel mutations. (2) c.1129G>C, p.Glu377Gln was a SNP but not a disease-causing mutation at least in Chinese population.

Arteriosclerosis ; complications ; genetics ; Base Sequence ; Child ; Child, Preschool ; DNA Helicases ; genetics ; Exons ; Humans ; Immunologic Deficiency Syndromes ; complications ; genetics ; Lymphopenia ; Male ; Mutation ; Mutation, Missense ; Nephrotic Syndrome ; complications ; genetics ; Osteochondrodysplasias ; complications ; congenital ; genetics ; Polymorphism, Single Nucleotide ; Pulmonary Embolism ; complications ; genetics ; Renal Insufficiency

BACKGROUND/AIMS: The aim of this study was to identify the profile of rare variants associated with Crohn's disease (CD) using whole exome sequencing (WES) analysis of Korean children with CD and to evaluate whether genetic profiles could provide information during medical decision making. METHODS: DNA samples from 18 control individuals and 22 patients with infantile, very-early and early onset CD of severe phenotype were used for WES. Genes were filtered using panels of inflammatory bowel disease (IBD)-associated genes and genes of primary immunodeficiency (PID) and monogenic IBD. RESULTS: Eighty-one IBD-associated variants and 35 variants in PID genes were revealed by WES. The most frequently occurring variants were carried by nine (41%) and four (18.2%) CD probands and were ATG16L2 (rs11235604) and IL17REL (rs142430606), respectively. Twenty-four IBD-associated variants and 10 PID variants were predicted to be deleterious and were identified in the heterozygous state. However, their functions were unknown with the exception of a novel p.Q111X variant in XIAP (X chromosome) of a male proband. CONCLUSIONS: The presence of many rare variants of unknown significance limits the clinical applicability of WES for individual CD patients. However, WES in children may be beneficial for distinguishing CD secondary to PID.
Asian Continental Ancestry Group/genetics ; Carrier Proteins/genetics ; Child ; Child, Preschool ; Crohn Disease/*genetics ; *Exome ; Female ; Genetic Predisposition to Disease ; *Genetic Variation ; Humans ; Immunologic Deficiency Syndromes/genetics ; Infant ; Male ; Phenotype ; Receptors, Interleukin-17/genetics ; Republic of Korea ; Sequence Analysis, DNA/*methods ; X-Linked Inhibitor of Apoptosis Protein/genetics

MonoMAC syndrome is a newly discovered immune deficiency syndrome caused by GATA-2 mutation, which is an autosomal dominant genetic disease. MonoMAC syndrome has typical immune cell abnormalities, with severe infection and is prone to develop into a hematological disease. Therapeutics for this disease mainly relies on symptomatic treatment and hematopoietic stem cell transplantation. In this paper, the research advances in clinical manifestations, laboratory tests, pathogenesis, diagnosis and treatment of MonoMAC syndrome are reviewed.
GATA2 Transcription Factor ; genetics ; Humans ; Immunologic Deficiency Syndromes ; genetics ; Monocytes ; pathology ; Mutation ; Mycobacterium Infections ; etiology ; Syndrome

ABO discrepancy refers to an inconsistency between red cell and serum typings and has various causes, including hypogammaglobulinemia. IgM deficiency is a rare disorder that may accompany several conditions such as infection and autoimmune disorders. Here, we describe a case of IgM deficiency discovered during the evaluation of an ABO discrepancy in a 16-yr-old Korean boy. ABO blood grouping showed that while his cell type was O+, serum typing detected only anti-A (3+). Anti-B was not detectable at room temperature but was graded at 1+ at 4degrees C. ABO genotyping revealed an O/O genotype. His serum IgG, IgA, and IgM concentrations were 770 mg/dL (reference range: 800-1,700 mg/dL), 244 mg/dL (reference range: 100-490 mg/dL), and 13.5 mg/dL (reference range: 50-320 mg/dL), respectively. He was diagnosed with acute osteomyelitis on the basis of clinical presentation and imaging studies. The symptoms gradually improved within 3 weeks of treatment. However, the ABO discrepancy and IgM deficiency persisted even 6 months after recovery and lymphocyte subset analysis revealed CD19+ B cell deficiency. To the best of our knowledge, IgM deficiency detected by ABO discrepancy in a patient with acute osteomyelitis has not been reported before.
ABO Blood-Group System/genetics ; Acute Disease ; Adolescent ; B-Lymphocytes/cytology/immunology/metabolism ; Bone and Bones/radionuclide imaging ; Genotype ; Humans ; Immunoglobulin A/blood ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Immunologic Deficiency Syndromes/complications/*diagnosis ; Knee/radionuclide imaging ; Magnetic Resonance Imaging ; Male ; Osteomyelitis/complications/*diagnosis ; Radiopharmaceuticals/diagnostic use

ABO discrepancy refers to an inconsistency between red cell and serum typings and has various causes, including hypogammaglobulinemia. IgM deficiency is a rare disorder that may accompany several conditions such as infection and autoimmune disorders. Here, we describe a case of IgM deficiency discovered during the evaluation of an ABO discrepancy in a 16-yr-old Korean boy. ABO blood grouping showed that while his cell type was O+, serum typing detected only anti-A (3+). Anti-B was not detectable at room temperature but was graded at 1+ at 4degrees C. ABO genotyping revealed an O/O genotype. His serum IgG, IgA, and IgM concentrations were 770 mg/dL (reference range: 800-1,700 mg/dL), 244 mg/dL (reference range: 100-490 mg/dL), and 13.5 mg/dL (reference range: 50-320 mg/dL), respectively. He was diagnosed with acute osteomyelitis on the basis of clinical presentation and imaging studies. The symptoms gradually improved within 3 weeks of treatment. However, the ABO discrepancy and IgM deficiency persisted even 6 months after recovery and lymphocyte subset analysis revealed CD19+ B cell deficiency. To the best of our knowledge, IgM deficiency detected by ABO discrepancy in a patient with acute osteomyelitis has not been reported before.
ABO Blood-Group System/genetics ; Acute Disease ; Adolescent ; B-Lymphocytes/cytology/immunology/metabolism ; Bone and Bones/radionuclide imaging ; Genotype ; Humans ; Immunoglobulin A/blood ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Immunologic Deficiency Syndromes/complications/*diagnosis ; Knee/radionuclide imaging ; Magnetic Resonance Imaging ; Male ; Osteomyelitis/complications/*diagnosis ; Radiopharmaceuticals/diagnostic use

OBJECTIVETo study the clinical and laboratory characteristics of cases with warts, hypogammaglobulinemia, infections and myelokathexis (WHIM) syndrome.

METHODAn 11-year-old boy was diagnosed as WHIM syndrome and CXCR4 gene mutation analysis was performed.

RESULTSince 3 years of age, the patient had recurrent fever and persistent cough. Since 6 years of age, he had warts on his fingers, the warts increased gradually. His complete blood count showed: white blood cell (WBC) 0.65×10(9)/L, neutrophil 0.15×10(9)/L, hemoglobin 116 g/L, platelet 200×10(9)/L, reticulocyte 0.62%. Results of serum biochemical tests: total protein (TP) 72.2 g/L (reference value 60 - 80 g/L), albumin 20.4 g/L (reference value 20 - 35 g/L), gammaglobulin 20.4 g/L (reference value 20 - 35 g/L). IgG 5.56 g/L (reference value 7.51 - 15.6 g/L), IgA 0.48 g/L (reference value 0.82 - 4.53 g/L), IgM 0.29 g/L (reference value 0.46 - 3.04 g/L). Peripheral blood lymphocyte subsets: CD3(+)T lymphocyte 43.6% (reference value 64.01% - 75.95%), CD19(+)B lymphocyte 1.00% (reference value 9.02% - 14.1%). Bone marrow smears showed that many of the neutrophils had a reactive appearance, with cytoplasmic vacuolation. Most neutrophils had hypersegmentation with four or five nuclear lobules. In some cells, the filaments connecting the nuclear lobes were long. CXCR4 mutation was detected.

CONCLUSIONWHIM syndrome is a rare immunodeficiency disorder with an autosomal-dominant pattern of inheritance. The disease is less progressive, and may accompany the patients' whole life.

Agranulocytosis ; genetics ; pathology ; Amino Acid Sequence ; Child ; Humans ; Immunoglobulins ; blood ; Immunohistochemistry ; Immunologic Deficiency Syndromes ; genetics ; pathology ; Leukocyte Count ; Male ; Mutation ; Receptors, CXCR4 ; genetics ; Warts ; genetics ; pathology