Humans ; Mutation ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/genetics*

PURPOSE: Dengue virus infection is now a global problem. Currently, there is no licensed vaccine or proven antiviral treatment against this virus. All four serotypes (1-4) of dengue virus can infect human. An effective dengue vaccine should be tetravalent to induce protective immune responses against all four serotypes. Most of dengue vaccine candidates are monovalent, or in the form of physically mixed multivalent formulations. Recently envelope protein domain III of virus is considered as a vaccine candidate, which plays critical roles in the most important viral activities. Development of a tetravalent protein subunit vaccine is very important for equal induction of immune system and prevention of unbalanced immunity. Here, we have presented and used a rational approach to design a tetravalent dengue vaccine candidate. MATERIALS AND METHODS: We designed a multi domain antigen by fusing four consensus domain III sequences together with appropriate hydrophobic linkers and used several types of bioinformatics software and neural networks to predict structural and immunological properties of the designed tetravalent antigen. RESULTS: We designed a tetravalent protein (EDIIIF) based on domain III of dengue virus envelope protein. According to the results of the bioinformatics analysis, the constructed models for EDIIIF protein were structurally stable and potentially immunogenic. CONCLUSION: The designed tetravalent protein can be considered as a potential dengue vaccine candidate. The presented approach can be used for rational design and in silico evaluation of chimeric dengue vaccine candidates.
Computational Biology ; Computer Simulation* ; Consensus ; Dengue Virus ; Dengue* ; Humans ; Immune System ; Protein Structure, Tertiary ; Protein Subunits ; Staphylococcal Protein A*

Female ; GTP-Binding Protein gamma Subunits ; genetics ; Humans ; Male ; Mutation ; Pedigree ; Silver-Russell Syndrome ; diagnosis ; genetics

OBJECTIVE: To explore the genetic basis for a child featuring global developmental delay. METHODS: DNA was extracted from peripheral blood sample taken from the patient and subjected to whole exome sequencing. Suspected variants were verified by Sanger sequencing of his family members. RESULTS: A heterozygous c.239T>C (p.Ile80Thr) variant of the GNB1 gene was detected in the proband, which was a verified to be de novo in origin. CONCLUSION The heterozygous c.239T>C (p.Ile80Thr) variant of the GNB1 gene probably underlay the disease in this child.
Arthrogryposis ; Child ; Family ; GTP-Binding Protein beta Subunits ; Heterozygote ; Humans ; Intellectual Disability/genetics* ; Whole Exome Sequencing

OBJECTIVE: To carry out genetic testing for a family affected with distal hereditary motor neuronopathy V (dHMN V). METHODS: Potential mutations of the GARS and BSCL2 genes were analyzed with PCR and Sanger sequencing. Suspected mutation was verified among unaffected members of the family and 100 healthy controls. Prenatal diagnosis was provided based on the above results. RESULTS: Sequencing analysis has identified a heterozygous c.269C>T (p.S90L) mutation in the BSCL2 gene, which resulted in replacement of Serine (TCG) to Leucine (TTG). The same mutation was found in all other 3 patients from the pedigree but not among unaffected members or the 100 healthy controls. By prenatal diagnosis, the fetus did not carry the above mutation. CONCLUSION Pathogenic mutation of BSCL2 gene probably underlies the dHMN V in this pedigree, which enabled prenatal diagnosis for the proband.
Female ; GTP-Binding Protein gamma Subunits ; Humans ; Muscular Atrophy, Spinal ; Mutation ; Pedigree ; Pregnancy

A girl, aged 1 year and 9 months, was found to have hypertriglyceridemia in the neonatal period, with unusual facies and signs of dark skin all over the body, disappearance of subcutaneous adipose, acanthosis nigricans of the neck, excessive and thick hair, empty cheeks, muscle hypertrophy of the extremities, hepatomegaly, and neutrophil deficiency. Whole exome sequencing of monogenic disorder revealed a homozygote mutation in the BSCL2 gene, c.974 (exon 7)_c.975 (exon 7) insG. Her parents were heterozygotes for this locus. The girl was diagnosed with congenital generalized lipodystrophy (CGL), but the association between CGL and neutrophil deficiency remained unclear. Triglyceride was maintained at a normal level after the treatment with a low-fat and high-carbohydrate diet, and there were no obvious changes in signs. CGL is a rare autosomal recessive systemic disease manifested as disappearance of systemic subcutaneous adipose, muscle hypertrophy of the extremities, and metabolic disorders in the neonatal period, such as high triglycerides, hyperinsulinemia, and hyperglycemia. About 95% of CGL cases are caused by mutations in the AGPAT2 or BSCL2 gene.
Facies ; Female ; GTP-Binding Protein gamma Subunits ; Humans ; Hypertriglyceridemia ; Infant ; Lipodystrophy, Congenital Generalized

Electrocardiography ; GTP-Binding Protein beta Subunits/genetics* ; Humans ; Mutation ; Pedigree ; Sick Sinus Syndrome/genetics*

The N-methyl-D-aspartate receptor (NMDAR) in central nerve system is mostly composed of GluN1 and GluN2 subunits. The classical NMDAR has been intensively studied. However, GluN3‑containing NMDAR is much less expressed and have atypical channel properties. Recently, accumulating evidences have revealed two types of GluN3‑containing NMDAR: glutamate-gated GluN1/GluN2/GluN3 NMDAR and glycine-gated GluN1/GluN3 NMDAR. The former may play important roles in regulating synapse maturation and pruning non-used synapses, and its elevated expression at the adult stage may alter synaptic reorganization in some neuropsychiatric disorders. The latter is expressed in the medial habenula and involves in control of aversion. This article reviews the recent progresses on the expression, functional properties of GluN3‑containing atypical NMDARs and the physiological and pathological relevance.
Central Nervous System/metabolism* ; Protein Subunits/metabolism* ; Receptors, N-Methyl-D-Aspartate ; Synapses

Pseudohypoparayhyroidism (PHP) is a rare autosomal dominant or recessive genetic disorder characterized by low calcium, high phosphorus, and target organ resistance to parathyroid. The clinical characteristics and genetic features in 4 patients with Type Ib PHP in the Third Xiangya Hospital, Central South University, have been reviewed. All 4 patients had low calcium, high phosphorus, and parathyroid resistance. Among them, 2 patients had slightly elevated thyroid stimulating hormone and mild features of Albright's hereditary osteodystrophy, and one patient had hypokalemia. No guanine nucleotide-binding protein alpha-stimulating activity polypeptide 1 (GNAS) and gene variant associated with hypokalemia were identified using the whole exome sequencing. The results of the methylation-specific multiple ligation-dependent probe amplification showed that there were abnormal methylation of the upstream differentially methylated regions of GNAS in the 4 patients. There were phenotype overlap among the various subtypes of PHP. Detection of GNAS gene methylation in patients with clinical suspicion of Type Ib PHP is helpful for the diagnosis and treatment of PHP.
Humans ; Chromogranins/genetics* ; GTP-Binding Protein alpha Subunits, Gs/genetics* ; Hypokalemia ; Calcium ; Pseudohypoparathyroidism/genetics* ; Phosphorus

Since the outbreak of corona virus disease 2019 (COVID-19), viral strains have mutated and evolved. Vaccine research is the most direct and effective way to control COVID-19. According to different production mechanisms, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines included inactivated virus vaccine, live attenuated vaccine, mRNA vaccine, DNA vaccine, viral vector vaccine, virus-like particle vaccine and protein subunit vaccine. Among them, viral protein subunit vaccine has a wide application prospect due to its high safety and effectiveness. Viral nucleocapsid protein has high immunogenicity and low variability which could be a new direction for vaccine production. We summarized the current development of vaccine research by reviewing the current progress, vaccine safety and vaccine immune efficiency. It is hoped that the proposed possible development strategies could provide a reference for epidemic prevention work in future.
Humans ; SARS-CoV-2/genetics* ; COVID-19/prevention & control* ; Protein Subunits ; Vaccines, DNA ; Nucleocapsid Proteins