Clinical characteristics and genetic analysis of four patients with central hypothyroidism due to IGSF1 gene variants / 中华医学遗传学杂志

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.

DNA methylation in human papillomavirus-infected cervical cells is elevated in high-grade squamous intraepithelial lesions and cancer / 부인종양

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.

DNA prime-protein boost based vaccination with a conserved region of leptospiral immunoglobulin-like A and B proteins enhances protection against leptospirosis

Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of theLeptospira genus. Vaccination with bacterins has severe limitations. Here, we evaluated the N-terminal region of the leptospiral immunoglobulin-like B protein (LigBrep) as a vaccine candidate against leptospirosis using immunisation strategies based on DNA prime-protein boost, DNA vaccine, and subunit vaccine. Upon challenge with a virulent strain ofLeptospira interrogans, the prime-boost and DNA vaccine approaches induced significant protection in hamsters, as well as a specific IgG antibody response and sterilising immunity. Although vaccination with recombinant fragment of LigBrep also produced a strong antibody response, it was not immunoprotective. These results highlight the potential of LigBrep as a candidate antigen for an effective vaccine against leptospirosis and emphasise the use of the DNA prime-protein boost as an important strategy for vaccine development.

MYC Rearrangement Involving a Novel Non-immunoglobulin Chromosomal Locus in Precursor B-cell Acute Lymphoblastic Leukemia

MYC rearrangement, a characteristic cytogenetic abnormality of Burkitt lymphoma and several subsets of other mature B-cell neoplasms, typically involves an immunoglobulin gene partner. Herein, we describe a case of precursor B-cell lymphoblastic leukemia harboring a MYC rearrangement with a novel non-immunoglobulin partner locus. The patient was a 4-yr-old Korean boy with ALL of the precursor B-cell immunophenotype. At the time of the second relapse, cytogenetic analyses revealed t(4;8)(q31.1;q24.1) as a clonal evolution. The MYC rearrangement was confirmed by FISH analysis. He died 3 months after the second relapse without achieving complete remission. To our knowledge, this is the first report of a case of MYC rearrangement with a non-immunoglobulin partner in precursor B-cell lymphoblastic leukemia.

Effect of TSLC1 gene on proliferation, invasion and apoptosis of human hepatocellular carcinoma cell line HepG2 / 华中科技大学学报（医学）（英德文版）

The recombinant plasmid pCI-TSLC1 carrying TSLC1 gene was stably transfected into human hepatocellular carcinoma cell line HepG2. Cell proliferation was analyzed by MTT assay. The ability of migration was determined by transwell and FACSort flow cytometry was used to detect the cell cycle distribution and apoptosis. Western blotting revealed that H4 expressed higher amounts of TSLC1 protein than H15 and H0 did. The growth of TSLC1-transfected cells was significantly suppressed in vitro, and the ability of migration was reduced as well. The re-expression of TSLC1 could induce cell apoptosis. It was concluded that TSLC1 strongly inhibited the growth and ability of migration of HepG2 cell line in vitro and also induced apoptosis, suggesting that TSLC1 could reduce the tumorigenicity of human hepatocellular carcinoma cell line HepG2 in vitro, which provided a basis for further exploring the roles of TSLC1 in hepatocellular cellular carcinoma.

Effective methods for the production of immunoglobulin Y using immunogens of Bordetella bronchiseptica, Pasteurella multocida and Actinobacillus pleuropneumoniae

Swine respiratory diseases induce severe economic losses in the swine industry worldwide. Several methods have been developed and applied to control these diseases. However, there are still problems of disease control in the swine industry. Recently, egg yolk antibodies have been found to offer several advantages for disease control in animals and humans. In a previous study (24), antibodies to several causative pathogens of swine respiratory diseases were developed. However, several problems remained, especially in terms of reduced laying rates. Therefore, experimental vaccines were reformulated with various bacterial antigens of the swine respiratory diseases. After immunizing hens with the antigens, antibody profiles and other effects including laying rates were investigated and compared to those of the previous study. Profiles of antibody titers were very similar with those of the previous study. However, side effects, such as depression, weakness, reduction of laying rates and mortality, were dramatically lowered and laying rates were increased in hens injected with certain experimental vaccines. In particular, laying rates of hens injected with vaccines against atrophic rhinitis were increased up to 84% by injecting a vaccine composed of only the DNTs of B. bronchiseptica and P. multocida D:4. Efficacies of the vaccines against swine pneumonic pasteurellosis and pleuropneumonia were very similar with those of the previous study. These results suggest that new vaccines could be effective in the production of egg yolk antibodies against the causative agents of swine respiratory diseases.

Conceptos de la herencia en la alergia / Concepts of heredity in allergy

Se presentan algunos conceptos sobre la herencia en la alergia; con base en ellos se pretende comprender cómo los procesos genéticos y ambientales que intervienen en las enfermedades alérgicas se combinan para producirlas. Se analizan los conceptos tradicionales y otros actuales sobre la síntesis de la inmunoglobulina E en los procesos alérgicos. También se menciona la susceptibilidad a medicamentos y sus consideraciones genéticas. Se concluye que la alergia es un estado familiar común al que se le ha asignado un gen representante: el cromosoma 11q13