OBJECTIVE: To explore the clinical manifestations and genetic characteristics of patients with congenital central hypothyroidism due to variants of IGSF1 gene. METHODS: Clinical data, results of genetic testing, and follow-up of four patients admitted to Children's Hospital of Soochow University during 2017 to 2021 were retrospectively analyzed. RESULTS: All of the four patients were males. Patient 1 had presented neonatal jaundice, patients 2 and 3 were admitted for growth retardation during childhood, and thyroid function test indicated slightly low free thyroxine (FT4), patient 4 was found to have reduced FT4 in the neonatal period. Genetic testing revealed that all of the four patients have harbored pathogenic variants of the IGSF1 gene, which were all inherited from their mothers. The thyroid functions in all patients were well controlled with oral levothyroxine and regular follow-up. CONCLUSION Pathogenic variants of the IGSF1 gene probably underlay the congenital central hypothyroidism with a variety of clinical manifestations, and genetic testing can facilitate the diagnosis at an early stage.
Child ; Male ; Infant, Newborn ; Female ; Humans ; Retrospective Studies ; Hypothyroidism/genetics* ; Genetic Testing ; Mothers ; Immunoglobulins/genetics* ; Membrane Proteins/genetics*

OBJECTIVE: To explore the mechanism of Haitongpi Prescription extract in the treatment of knee osteoarthritis based on transcriptome. METHODS: Total of 12 SPF grade rats were divided into control group(group C), model group(group M), and Haitongpi prescription group(group HP). The knee osteoarthritis rat model was established using the Panicker method for group M and group HP, and group HP was intervened by local topical application of Haitongpi Prescription extract for 4 weeks. Total RNA from mouse knee cartilage was extracted and three sets of differential genes were obtained through sequencing.Differential genes were prediction and analysis through GO function and KEGG pathway enrichment analysis. RESULTS: A total of 109 differentially expressed genes were identified in Group C versus Group M, while 118 differentially expressed genes were identified in Group M versus Group HP, resulting in a total of 28 genes. GO functional enrichment analysis showed that the mechanism of HP extract in treating knee osteoarthritis mainly involved immunoglobulin mediated immune response, immunoglobulin complexes, and antigen binding; KEGG pathway enrichment analysis showed correlation with tumor necrosis factor (TNF) signaling pathway, interleukin 17(IL-17) signaling pathway, and estrogen signaling pathway. CONCLUSION HP extract can exert therapeutic effects on knee osteoarthritis through mechanisms such as immunoglobulin mediated immune response, immunoglobulin complexes, and antigen binding, as well as signaling pathways such as TNF signaling pathway, IL-17 signaling pathway, and estrogen signaling pathway.
Mice ; Rats ; Animals ; Osteoarthritis, Knee/genetics* ; Transcriptome ; Interleukin-17 ; Ointments ; Estrogens ; Immunoglobulins

Aim: To identify the key risk factors of intrauterine hepatitis B virus transmission (HBV) and its effect on the placenta and fetus. Methods: 425 infants born to hepatitis B surface antigen (HBsAg)-positive pregnant women who received combined immunization with hepatitis B immunoglobulin and hepatitis B vaccine between 2009 to 2015 were prospectively enrolled in this study. The intrauterine transmission situation was assessed by dynamic monitoring of infants HBV DNA load and quantitative HBsAg. Univariate and multivariate regression analysis was used to determine the high risk factors for intrauterine transmission. Stratified analysis was used to determine the relationship between maternal HBV DNA load and fetal distress. Transmission electron microscopy was used to observe HBV Effects on placental tissue. Results: HBV intrauterine infection rate was 2.6% (11/425). Multivariate analysis result showed that the maternal HBV DNA load was an independent risk factor for intrauterine infection among infants (P=0.011). Intrauterine infection and distress rate was significantly higher in infants with with maternal HBV DNA>10⁶ IU/ml than those with HBV DNA <10⁶ IU/ml (12.2% vs. 1.8%; χ²=11.275, P=0.006), and (24.4% vs. 16.0%, χ²=3.993, P=0.046). Transmission electron microscopy showed that mitochondrial edema, endoplasmic reticulum expansion and thicker basement membrane were apparent when the maternal HBV DNA>10⁶ IU/ml than that of maternal HBV DNA<10⁶ IU/ml (960 nm vs. 214 nm, Z=-2.782, P=0.005) in the placental tissue. Conclusion: Maternal HBV DNA>10⁶ IU/ml is associated not only with intrauterine infection, but also with increased incidence of intrauterine distress and placental sub-microstructural changes, providing strong clinical and histological evidence for pregnancy avoidance and treatment in this population.
DNA, Viral ; Female ; Fetal Distress/drug therapy* ; Hepatitis B/prevention & control* ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines/therapeutic use* ; Hepatitis B virus/genetics* ; Humans ; Immunoglobulins/therapeutic use* ; Infant ; Infectious Disease Transmission, Vertical/prevention & control* ; Placenta ; Pregnancy ; Pregnancy Complications, Infectious

Carcinoma, Renal Cell ; Disease Progression ; Humans ; Immunoglobulins/genetics* ; Kidney Neoplasms ; Membrane Proteins/genetics* ; Sialic Acid Binding Immunoglobulin-like Lectins

Enterovirus 71 frequently involves the central nervous system and may present with a variety of neurologic manifestations. Here, we aimed to describe the clinical features, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) profiles of patients presenting with neurologic complications of enterovirus 71 infection. We retrospectively reviewed the records of 31 pediatric patients hospitalized with acute neurologic manifestations accompanied by confirmed enterovirus 71 infection at Ulsan University Hospital between 2010 and 2014. The patients' mean age was 2.9 ± 5.5 years (range, 18 days to 12 years), and 80.6% of patients were less than 4 years old. Based on their clinical features, the patients were classified into 4 clinical groups: brainstem encephalitis (n = 21), meningitis (n = 7), encephalitis (n = 2), and acute flaccid paralysis (n = 1). The common neurologic symptoms included myoclonus (58.1%), lethargy (54.8%), irritability (54.8%), vomiting (48.4%), ataxia (38.7%), and tremor (35.5%). Twenty-five patients underwent an MRI scan; of these, 14 (56.0%) revealed the characteristic increased T2 signal intensity in the posterior region of the brainstem and bilateral cerebellar dentate nuclei. Twenty-six of 30 patients (86.7%) showed CSF pleocytosis. Thirty patients (96.8%) recovered completely without any neurologic deficits; one patient (3.2%) died due to pulmonary hemorrhage and shock. In the present study, brainstem encephalitis was the most common neurologic manifestation of enterovirus 71 infection. The characteristic clinical symptoms such as myoclonus, ataxia, and tremor in conjunction with CSF pleocytosis and brainstem lesions on MR images are pathognomonic for diagnosis of neurologic involvement by enterovirus 71 infection.
Acute Disease ; Brain/diagnostic imaging ; Central Nervous System Diseases/etiology/*pathology ; Child ; Child, Preschool ; Encephalitis/pathology ; Enterovirus A, Human/genetics/*isolation & purification ; Enterovirus Infections/drug therapy/*pathology/virology ; Feces/virology ; Female ; Humans ; Immunoglobulins/administration & dosage ; Infant ; Injections, Intravenous ; Leukocytes/cytology ; Leukocytosis/cerebrospinal fluid/pathology ; Magnetic Resonance Imaging ; Male ; RNA, Viral/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Republic of Korea ; Retrospective Studies ; Seasons

OBJECTIVE: DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. METHODS: A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. RESULTS: Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). CONCLUSION: DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies.
Alphapapillomavirus/genetics ; *Atypical Squamous Cells of the Cervix/pathology/virology ; Cell Adhesion Molecules/genetics ; *DNA Methylation ; Female ; Genotype ; Humans ; Immunoglobulins/genetics ; Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics ; Paired Box Transcription Factors/genetics ; Papanicolaou Test ; Pituitary Adenylate Cyclase-Activating Polypeptide/genetics ; ROC Curve ; Squamous Intraepithelial Lesions of the Cervix/*genetics/pathology/virology ; Uterine Cervical Neoplasms/*genetics/pathology/virology ; Vaginal Smears

OBJECTIVETo explore the application of BIOMED- 2 standardized immunoglobulin (Ig) gene rearrangement system in the diagnosis of multiple myeloma (MM), and the significance of clonality analysis by multiplex-PCR amplifications.

METHODSA total of 167 cases of MM bone marrow samples from 2009 to 2013, and 20 cases of reactive plasmacytosis used as the controls were included in this study. Multiplex-PCR amplifications were performed and the Ig gene rearrangements were analyzed using BIOMED-2 standardized clonality analysis system.

RESULTS① Of 167 MM cases, 107 showed IgH VH-JH rearrangement, 33 showed IgH DH-JH rearrangement, and 30% showed IgH DH-JH rearrangement in 60 IgH VH-JH rearrangement negative MM cases. The difference was statistically significant between IgH VH-JH rearrangement positive and negative cases (14.0% vs 30.0%, P=0.032). The total positive rate of IgH VH-JH, IgH DH-JH and IgK was 94.6%. The 20 reactive plasmacytosis (RP) cases showed negative Ig gene rearrangement. 2 of 167 MM cases, 9 (5.4%) showed clonal IgH rearrangement by agarose electrophoresis were confirmed as polyclonality by capillary electrophoresis. ③ Of 53 MM cases who have been detected by Ig gene rearrangement system and fluorescence in situ hybridization (FISH) for IgH simultaneously, 36 showed IgH rearrangement, 26 showed FISH IgH positive, and the difference was statistically significant (67.9% vs 49.1%, P=0.049).

CONCLUSIONCombined detection of IgH VH- JH, IgH DH- JH and IgK could improve the positive rate of MM clonality dramatically, and measurement of IgH DH-JH rearrangement was more important in the IgH VH- JH negative cases. Ig gene rearrangement system was a faster and more sensitive method than FISH IgH. Application of BIOMED- 2 standardized immunoglobulin (Ig) gene rearrangement system is of significance for MM diagnosis.

Humans ; Immunoglobulins ; genetics ; In Situ Hybridization, Fluorescence ; Multiple Myeloma ; diagnosis ; genetics ; Polymerase Chain Reaction ; V(D)J Recombination

OBJECTIVETo study the expression and significance of tumor suppressor in lung cancer 1 (TSLC1) gene methylation, the expression of TSLC1 protein in cervix cancer and precancerous lesions as well as their relationship with HR-HPV DNA infection.

METHODSThe clinicopathological data of 92 cases of different cervical lesions during March 2011 to August 2012 treated in our hospital were collected. There were pathologically confirmed 10 cases of normal cervix, 26 cases of cervical intraepithelial neoplasia (CIN) I, 20 cases of CIN II, 15 cases of CIN III, and 21 cases of cervical cancer. Methylation-specific polymerase chain reaction (MSP) was used to detect the TSLC1 gene methylation status in cervical lesions, immunohistochemistry (SP) was used to detect the expressions of TSLC1 protein in cervical lesions, and the second generation hybrid capture (HC2) method was used to detect the high-risk HPV in cervical lesions.

RESULTSThe expression rate of TSLC1 gene methylation in normal cervical tissue, CIN I, CIN II, CIN III and SCC were 10.0%, 30.8%, 55.0%, 60.0%, 66.7%, respectively, showing a statistically significant difference (P = 0.004). The positive expression rate of TSLC1 protein in normal cervical tissue, CIN I, CIN II, CIN III and SCC were 100.0%, 80.8%, 65.0%, 33.3%, and 23.8%, respectively, with a significant difference (P = 0.004). In the progression from CIN to invasive cervical cancer, there was no significant correlation between TSLC1 gene methylation and HR-HPV DNA infection (P = 0.919), TSLC1 protein expression and HR-HPV DNA infection (P = 0.664). The correlation analysis showed a negative correlation between TSLC1 gene methylation and TSLC1 protein expression (r = -0.674, P < 0.001).

CONCLUSIONSTSLC1 gene promoter methylation may be an early event in the cervical carcinogenesis, become an early sensitive marker, and serve the early prevention and prognostic prediction for cervical cancer.

Cell Adhesion Molecule-1 ; Cell Adhesion Molecules ; genetics ; metabolism ; Cervical Intraepithelial Neoplasia ; genetics ; metabolism ; DNA Methylation ; Disease Progression ; Female ; Humans ; Immunoglobulins ; genetics ; metabolism ; Immunohistochemistry ; Methylation ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Uterine Cervical Neoplasms ; genetics ; metabolism

OBJECTIVETo investigate the clinical and immunological laboratory features, gene mutations, treatment and prognosis in children with Wiskott-Aldrich syndrome (WAS).

METHODThe clinical, laboratory characteristics, treatment and prognosis of 132 children with WAS, who visited Children's Hospital of Chongqing Medical University from April 2000 to June 2015, were analyzed retrospectively.

RESULTAll patients were male. The median age of disease onset was 15 days and the median age at diagnosis was 10 months. Of the 132 cases, 112 had classic WAS, 20 had X-linked thrombocytopenia (XLT). The median platelet count was 23×10(9)/L. All cases had the clinical characteristics of WAS including bleeding, eczema, and being susceptible to infection. The initial symptoms include hemorrhage (75.0%) and eczema (16.7%). Twenty-one cases had autoimmune diseases and one patient had leukemia. WAS protein (WASP) expression in 115 cases were measured by flow cytometry, 88 cases were negative, in 12 cases WASP decreased, in 5 cases it was normal, 10 cases had bimodal distribution. Eighty-one kinds of mutations were found in 122 families, including eight kinds of hot-spot mutations, which were 290 C> N / 291G> N (R86C / H / L), 665 C> T (R211X), 155 C> T (R41X), 168 C> T (T45 M), IVS1+ 1 g> t/ a, IVS6 + 5 g> a, IVS8 + 1 g> a and IVS8 + 1to + 6del gtga. Meantime, 29 kinds of novel mutations were found, which were 321T>C, 415C>A, 471C>T, 102-105delC, 521 del C, 1330 del A, IVS2-2 a>c, 168 C>A/1412 C> T, exon1-2 del/1412 C>T, and so on. The proportion of CD3(+) T cells (31.3%), helper T cells (37.3%) and cytotoxic T cells (38.6%) in the peripheral blood declined. The serum levels of IgG (51.1%), IgA (43.3%) and IgE (40.0%) increased, IgM (25.6%) decreased. Of the 132 cases, 72 remain survived, of whom 36 cases received hematopoietic stem cell transplantation (HSCT), 14 patients with classic WAS received intravenous immunoglobulin (IVIG) therapy. With regular IVIG therapy, the frequency of infections was reduced and the patients' symptoms were improved.

CONCLUSIONThe clinical characteristics of Wiskott-Aldrich syndrome were early age of onset, microthrombocytopenia, eczema and recurrent infections. The proportion of T lymphocyte declined, the serum levels of IgG, IgA, and IgE increased, and level of IgM decreased in a part of patients. The detection of WAS gene mutation and WAS protein detection was the key diagnostic methods. Regular IVIG can gain more time for children who will receive HSCT and improve their quality of life.

Genetic Diseases, X-Linked ; genetics ; Genotype ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunoglobulins, Intravenous ; therapeutic use ; Infant ; Infant, Newborn ; Male ; Mutation ; Platelet Count ; Retrospective Studies ; Thrombocytopenia ; genetics ; Wiskott-Aldrich Syndrome ; genetics ; Wiskott-Aldrich Syndrome Protein ; genetics

In order to perform large-scale genetic studies of Kawasaki disease (KD) in Korea, the Korean Kawasaki Disease Genetics Consortium (KKDGC) was formed in 2008 with 10 hospitals. Since the establishment of KKDGC, there has been a collection of clinical data from a total of 1198 patients, and approximately 5 mL of blood samples per patient (for genomic deoxyribonucleic acid and plasma isolation), using a standard clinical data collection form and a nation-wide networking system for blood sample pick-up. In the clinical risk factor analysis using the collected clinical data of 478 KD patients, it was found that incomplete KD type, intravenous immunoglobulin (IVIG) non-responsiveness, and long febrile days are major risk factors for coronary artery lesions development, whereas low serum albumin concentration is an independent risk factor for IVIG non-responsiveness. In addition, we identified a KD susceptibility locus at 1p31, a coronary artery aneurysm locus (KCNN2 gene), and the causal variant in the C-reactive protein (CRP) promoter region, as determining the increased CRP levels in KD patients, by means of genome-wide association studies. Currently, this consortium is continually collecting more clinical data and genomic samples to identify the clinical and genetic risk factors via a single nucleotide polymorphism chip and exome sequencing, as well as collaborating with several international KD genetics teams. The consortium-based approach for genetic studies of KD in Korea will be a very effective way to understand the unknown etiology and causal mechanism of KD, which may be affected by multiple genes and environmental factors.
Aneurysm ; C-Reactive Protein ; Coronary Vessels ; Data Collection ; DNA ; Exome ; Genetics* ; Genome-Wide Association Study ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Korea* ; Mucocutaneous Lymph Node Syndrome* ; Plasma ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Risk Factors ; Serum Albumin