Objective: To report the clinical features and genetic variations of monogenic lupus caused by DNASE1L3 deficiency and to introduce preliminary experience on diagnosis and treatment for this disease. Methods: Clinical data of 3 children from the same pedigree were collected who were diagnosed with DNASE1L3 defect-associated monogenic lupus in August 2020 by Department of Pediatrics, Peking Union Medical College Hospital referred from Department of Pediatrics, Boai Hospital of Zhongshan. DNA was extracted from the peripheral blood of the patients and their parients to perform genetic analysis and confirmation. Six interferon-stimulated genes were relatively quantified to examine the activation of the type I interferon signaling. "DNASE1L3" "systemic lupus erythematosus" and "SLE" were searched in PubMed, Wangfang Data, CNKI databases for related reports from database established date to June 2022. Spectrum of genetic variations and clinical phenotypes were analyzed in combination with this pedigree. Results: Case 1, a 14-year-old girl with edema, hematuria, and heavy proteinuria, presented with membranous nephropathy. Case 2, the 12-year-old younger brother of case 1 with hematologic, cardiac, pulmonary, renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody and low complement C3, manifested with systemic lupus erythematosus. Case 3, the 8-year-old younger sister of case 1 with hematologic, cardiac, pulmonary and renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody, and low complement C3 and C4, manifested with systemic lupus erythematosus. Genetic testing revealed that all 3 patients carried homozygous deletions in exons 3 and 4 on DNASE1L3 gene. Interferon scores were elevated in case 1, 2 and their parents but normal in case 3. All 3 patients were diagnosed with monogenic lupus caused by DNASE1L3 defects. Literature searching identified 10 relevant publications in English and 0 publication in Chinese, involving 42 patients from 18 pedigrees (including the 3 cases from this pedigree). Nine variants were found: c.289_290delAC (p.T97Ifs*2), c.643delT (p.W215Gfs*2), c.320+4delAGTA, c.321-1G>A, Ex5 del, c.433G>A, c.581G>A (p.C194Y), c.537G>A (p.W179X), and Ex3-4 del. The hotspot variants were c.643delT (43% (36/84)) and c.289_290delAC (36% (30/84)). Kidney was affected in 31 cases (74%) of the 42 cases. Among the 25 patients, joints were affected in 16 cases (64%), fever were reported in 13 cases (52%) hematologic system was involved 13 cases (52%), rash was present in 10 cases (40%), intestinal tract was involved in 8 cases (32%), lungs were involved in 6 cases (24%), eyes were involved in 4 cases (16%), and the heart was involved in 4 cases (16%). The 2 cardiopulmonary affected patients from literature showed poor prognosis, with 1 died, and 1 right heart failure. Conclusions: The clinical manifestations of monogenic lupus caused by DNASE1L3 defect are highly heterogenous, primarily with renal, blood, joint, intestinal, and cardiopulmonary involvement. There is no correlation between the genotype and the phenotype. DNASE1L3 defects were predominantly mediated by null varations including nonsense, splicing, frameshift and exon deletions. The hotspot variants are c.643delT and c.289_290delAC. DNASE1L3 defects should be cautioned in early-onset lupus-like patients with renal, joint and hematologic involvement. Cardiopulmonary involved patients require close monitoring for poor prognosis. Copy number variations should be carefully analyzed after negative whole exome sequencing.
Male ; Child ; Humans ; Homozygote ; Complement C3 ; Antibodies, Antinuclear ; DNA Copy Number Variations ; Sequence Deletion ; Interferons ; Lupus Erythematosus, Systemic/genetics* ; Antiviral Agents ; Endodeoxyribonucleases

Animals ; CRISPR-Cas Systems ; Endodeoxyribonucleases ; genetics ; metabolism ; Gene Editing ; methods ; Mice ; Transcription Activator-Like Effector Nucleases ; genetics ; metabolism

Meiotic recombination is carried out through a specialized pathway for the formation and repair of DNA double-strand breaks (DSBs) made by the Spo11 protein. The present study shed light on the functional role of cyclin, CYC2, in Tetrahymena thermophila which has transcriptionally high expression level during meiosis process. Knocking out the CYC2 gene results in arrest of meiotic conjugation process at 2.5-3.5 h after conjugation initiation, before the meiosis division starts, and in company with the absence of DSBs. To investigate the underlying mechanism of this phenomenon, a complete transcriptome profile was performed between wild-type strain and CYC2 knock-out strain. Functional analysis of RNA-Seq results identifies related differentially expressed genes (DEGs) including SPO11 and these DEGs are enriched in DNA repair/mismatch repair (MMR) terms in homologous recombination (HR), which indicates that CYC2 could play a crucial role in meiosis by regulating SPO11 and participating in HR.
Cell Cycle Checkpoints ; Cyclins ; genetics ; metabolism ; DNA Breaks, Double-Stranded ; DNA Mismatch Repair ; DNA Repair ; Endodeoxyribonucleases ; genetics ; metabolism ; Homologous Recombination ; Meiosis ; Microscopy, Fluorescence ; Phenotype ; Protozoan Proteins ; genetics ; metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, RNA ; Tetrahymena thermophila ; genetics ; metabolism ; Transcriptome

OBJECTIVE: To investigate the interaction between polymorphism of Toll-like receptor 4 (TLR4) gene G11367C in 3' untranslated region (UTR) and inhibitor of nuclear factor kappaB (IκB)-α 
Hae III in acute pancreatitis (AP) and the degree of severity.
 METHODS: A total of 450 patients with confirmed AP (AP group), who came from the First Affiliated Hospital of Xinxiang Medical College from May 2013 to June 2015, were divided into a mild AP subgroup (MAP subgroup), a moderately severe AP (MSAP subgroup), and a severe acute AP (SAP subgroup) (n=150 in each group). One hundred fifty healthy persons were served as a control group. There was no significant difference in age, gender, ethnicity and birthplace among all groups. The genetic polymorphisms of TLR4 gene G11367C in 3' untranslated region and IκB-α Hae III were analyzed by polymerase chain reaction (PCR). Eligible participants were personally interviewed by a questionnaire. Unconditional logistic regression model and single factor analysis were performed to calculate the adjusted odds ratios (OR) and 95% confidence intervals (95% CI) of G11367C and IκB-α Hae III polymorphisms, respectively. The interaction of nucleotide polymorphisms was analyzed.
 RESULTS: The frequencies of G11367C (GC), IκB-α Hae III (AG) and IκB-α Hae III (GG) were 69.56%, 33.78% and 36.22% in the AP group; 49.33%, 24.67% and 26.00% in the MAP subgroup; 70.67%, 34.67% and 36.67% in the MSAP subgroup; 88.67%, 42.00% and 46.00% in the SAP subgroup and 26.67%, 14.00% and 14.67% in the control group, respectively. There was significant difference in the frequencies betweenc the AP group and the control group, or among each AP subgroup (all P<0.01). The risk of AP was significantly increased in the subjects with G11367C (GC) genotype (ORAP=6.2828, ORMAP=2.6776, ORMSAP=6.6250, ORSAP=21.5147), which was also increased in those with IκB-α Hae III (AG) genotype (ORAP=5.7369, ORMAP=2.5277, ORMSAP=6.1824, ORSAP=17.8572) and in those with IκB-α Hae III (GG) genotype (ORAP=5.8724, ORMAP=2.5902, ORMSAP=6.4027, ORSAP=18.9022). The combined analysis of the polymorphisms showed that the percentage of G11367C (GC)/ IκB-α Hae III (GG) in the AP group, the MAP subgroup, the MSAP subgroup, the SAP subgroup and the control groups was 26.44%, 12.67%, 26.00%, 40.67% and 4.00%, respectively, with significant difference in the frequency among all groups (all P<0.01). The people who carried with Pro12Ala (AA)/Pro198Leu (LL) had a high risk of AP (ORAP=30.1314, ORMAP=6.7612, ORMSAP=39.5000, ORSAP=401.5833), and the statistical analysis suggested a positive interaction between Pro12Ala (AA) and Pro198Leu (LL) in increasing the risk of AP (All γ>1). Similarly, there were also positive interactions in the pathogenesis of AP between G11367C (GC) and IκB-α Hae III (AG) (All γ>1). 
 CONCLUSION These carriers of G11367C(GC), IκB-α Hae III(AG) and IκB-α Hae III (GG) genotypes may have a high risk of AP occurency, and there are significant interactions between genetic polymorphisms of G11367C and IκB-α Hae III, which increaes the risk of the occurrence and development of AP.
3' Untranslated Regions ; Acute Disease ; Deoxyribonucleases, Type II Site-Specific ; Ethnic Groups ; Genetic Predisposition to Disease ; Genotype ; Humans ; I-kappa B Kinase ; Logistic Models ; NF-KappaB Inhibitor alpha ; Odds Ratio ; Pancreatitis ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Toll-Like Receptor 4

OBJECTIVETo assess the association of vitamin D receptor gene (VDR) Apa I, Bsm I genotypes and allele frequencies and mild cognitive impairment (MCI) among elderly ethnic Uygurs from Xinjiang, China.

METHODSThe polymorphisms of the VDR genotypes (Apa I and Bsm I) were analyzed by the SNaPshot method in 124 MCI patients and 124 controls.

RESULTSFactors which can increase the risk for MCI have included the A allele of the Apa I polymorphism [OR=1.62, 95%CI(1.13-2.31)] and the AA genotype [OR=3.49, 95% CI(1.57-7.74)], the T allele of the Bsm I polymorphism [OR=1.94, 95%CI(1.24-3.05)], higher triglyceride and systolic blood pressure levels.

CONCLUSIONPolymorphisms of the VDR gene including the A allele and AA genotype of Apa I, and the T allele of Bsm I are probably associated with MCI among elderly ethnic Uygurs, and so are higher levels of triglyceride and systolic blood pressure.

Aged ; Alleles ; Asian Continental Ancestry Group ; genetics ; Binding Sites ; genetics ; Blood Pressure ; China ; Cognitive Dysfunction ; ethnology ; genetics ; psychology ; Deoxyribonucleases, Type II Site-Specific ; metabolism ; Diagnostic and Statistical Manual of Mental Disorders ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; ethnology ; genetics ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Polymorphism, Single Nucleotide ; Receptors, Calcitriol ; genetics ; Triglycerides ; blood

OBJECTIVETo explore the possible roles of polymorphisms of SPO11 and glutathionine S-transferase (GST) genes in idiopathic male infertility in a ethnic Han Chinese population from Henan.

METHODSMultiplex PCR and DNA sequencing were performed to determine the SPO11 c.517C>T(rs28368082) and GST genes (GSTM1, GSTT1, GSTP1) polymorphisms in 216 idiopathic male infertility cases and 198 normal samples.

RESULTSThe frequencies of the SPO11 CC and CT genotypes were 87.5% (189/216) and 12.5% (27/216) in the patients, and 97.5% (193/198) and 2.5% (5/198) in the controls, respectively. The frequencies of SPO11 CC and CT genotypes, the A>G transition at nucleotide 313 in the exon 5 of the GSTP1 gene, and the frequencies of combined genotypes GSTM1 (-/-), GSTT1 (+/+), GSTP1 (AA) and SPO11 (CT) were significantly different between the two groups (P<0.05).

CONCLUSIONThe rs28368082 polymorphism of the SPO11 gene, the A>G transition at nucleotide 313 in the exon 5 of the GSTP1 gene, and the combined genotypes of GSTM1 (-/-), GSTT1 (+/+), GSTP1 (AA) and SPO11 (CT) may be associated with idiopathic male infertility in ethnic Han Chinese.

Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Endodeoxyribonucleases ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; ethnology ; genetics ; Genotype ; Glutathione S-Transferase pi ; genetics ; Glutathione Transferase ; genetics ; Humans ; Infertility, Male ; enzymology ; ethnology ; genetics ; Linkage Disequilibrium ; Male ; Mutation ; Odds Ratio ; Polymorphism, Genetic ; Sequence Analysis, DNA

OBJECTIVENephrolithiasis is one of the most common disorders of the urinary tract. The aim of this study was to examine a possible relationship between DNase I/II activity and E3 SUMO-protein ligase NSE2 in the sera of nephrolithiasis patients to evaluate the possibility of a new biomarker for evaluating kidney damage.

METHODSSixty nephrolithiasis patients and 50 control patients were enrolled in a case-control study. Their blood urea, creatinine, protein levels and DNase I/II activity levels were measured by spectrometry. Serum NSMCE2 levels were measured by ELISA. Blood was collected from patients of the government health clinics in Kuantan-Pahang and fulfilled the inclusion criteria.

RESULTSThe result indicated that mean levels of sera NSMCE2 have a significantly increase (P<0.01) in patients compared to control group. Compared with control subjects, activities and specific activities of serum DNase I and II were significantly elevated in nephrolithiasis patients (P$lt;0.01).

CONCLUSIONThis study suggests that an increase in serum concentrations of DNase I/II and E3 SUMO-protein ligase NSE2 level can be used as indicators for the diagnosis of kidney injury in patients with nephrolithiasis.

Adult ; Blood Proteins ; analysis ; Case-Control Studies ; Creatinine ; blood ; Deoxyribonuclease I ; blood ; Endodeoxyribonucleases ; blood ; Hemoglobins ; analysis ; Humans ; Ligases ; blood ; Malaysia ; Middle Aged ; Nephrolithiasis ; blood ; enzymology ; Urea ; blood

OBJECTIVETo investigate the single nucleotide polymorphisms (SNPs) at interleukin 6 (IL-6)-174 and TNF-β NcoI in Chinese Han children in Guangzhou, China and to provide basic information for study on the association between IL-6-174 and TNF-β NcoI polymorphisms and systemic inflammatory response syndrome (SIRS).

METHODSAllele-specific polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism were used to determine the SNPs at IL-6-174 and TNF-β NcoI in 481 children selected from the Han population in Guangzhou in 2012. Genotype analysis and comparison with other populations were made with reference to relevant literature.

RESULTSChinese Han children in Guangzhou had only GG genotype at IL-6-174, and the SNP at this locus was rare or not seen in the Han population in Guangzhou. At TNF-β NcoI, the frequencies of TNF-β 1*1, TNF-β 1*2, and TNF-β 2*2 genotypes were 24.7%, 49.7%, and 25.6%, respectively. The sample distribution was in accordance with Hardy-Weinberg equilibrium. The TNF-β 1 allele frequency was significantly higher in Guangzhou Han population than in European and American white population (P<0.05).

CONCLUSIONSTNF-β NcoI SNP is prevalent in the Han population in Guangzhou, and the distribution of alleles is significantly different from that in the white population. The sample from an Hardy-Weinberg equilibrium population can be further used for study on the association between TNF-β NcoI SNP and SIRS in Chinese Han children in Guangzhou. IL-6-174 SNP is rare or not seen in the Han population in Guangzhou, so SNP at this locus cannot be selected for disease association analysis.

Asian Continental Ancestry Group ; genetics ; Child, Preschool ; China ; ethnology ; Deoxyribonucleases, Type II Site-Specific ; metabolism ; Female ; Gene Frequency ; Humans ; Interleukin-6 ; genetics ; Lymphotoxin-alpha ; genetics ; Male ; Polymorphism, Single Nucleotide ; Systemic Inflammatory Response Syndrome ; genetics

To reveal the effect of rotation cropping and bacterial manure on the growth of Chrysanthemum morifolium and screen the beneficial endophytic, the diversity of endophytic and dominant genera of different treatment groups were analyzed. Four different treatments were continuous cropping, rotation, self-made organic fertilizer and commercially available fertilizer, respectively. Endophytic bacterial diversity and dominant genera in different organs were examined using Terminal Restriction Fragment Length Polymorphism (T-RFLP). The results showed that enzyme Hae III was more appropriate than enzyme Hinfl because the number of TRFs digested by enzyme Hae III was more than that of enzyme Hinfl. In comparison of diversity, the endophytic bacterial communities' diversity index in group of cropping rotation and fertilizer was higher than that of continuous cropping which indicated that the addition of exogenous microorganism in soil could increase the diversity of plant endophyte. 18 dominant species were selected, including 3 kinds of Firmicutes, 4 kinds of Actinomycetes and 11 kinds of Proteobacteria. The results of dominant species comparison showed that the number of dominant species in continuous cropping of Ch. morifolium was significantly less than that of the rotation group. Some dominant bacteria in rotation group and fertilizer group such as Arthrobacter, Streptomyces, Streptomyces, Flavobacterium and Mycobacterium were not found in the continuous cropping of Ch. mortfolium group. Dominant species of fertilizer treatment group was similar with the rotation group, and the continuous cropping group's dominant species was more abundant. It indicates that these bacteria may be able to mitigate hindrance in continuous cropping, especially the Flavobacterium which can decompose the pathogenic fungi is worthy of further attention. Compared with leaves, there are more dominant species in roots and stems. The diversity of edophytic bacterial communities in continuous cropping of Ch. morifolium stays below than that in the rotation of Ch. morifolium, and fertilizer treatment can increase the diversity of continuous cropping so that it could mitigate hindrance in continuous cropping.
Actinobacteria ; physiology ; Agriculture ; Biodiversity ; Chrysanthemum ; growth & development ; microbiology ; Deoxyribonucleases, Type II Site-Specific ; Endophytes ; Fertilizers ; Gram-Positive Bacteria ; physiology ; Phylogeny ; Plant Leaves ; Plant Roots ; microbiology ; Polymorphism, Restriction Fragment Length ; Proteobacteria ; physiology ; RNA, Ribosomal, 16S ; chemistry ; genetics ; Soil ; Soil Microbiology

DraIII is a type IIP restriction endonucleases (REases) that recognizes and creates a double strand break within the gapped palindromic sequence CAC↑NNN↓GTG of double-stranded DNA (↑ indicates nicking on the bottom strand; ↓ indicates nicking on the top strand). However, wild type DraIII shows significant star activity. In this study, it was found that the prominent star site is CAT↑GTT↓GTG, consisting of a star 5' half (CAT) and a canonical 3' half (GTG). DraIII nicks the 3' canonical half site at a faster rate than the 5' star half site, in contrast to the similar rate with the canonical full site. The crystal structure of the DraIII protein was solved. It indicated, as supported by mutagenesis, that DraIII possesses a ββα-metal HNH active site. The structure revealed extensive intra-molecular interactions between the N-terminal domain and the C-terminal domain containing the HNH active site. Disruptions of these interactions through site-directed mutagenesis drastically increased cleavage fidelity. The understanding of fidelity mechanisms will enable generation of high fidelity REases.
Amino Acid Sequence ; Base Sequence ; Calorimetry, Differential Scanning ; Catalytic Domain ; Crystallography, X-Ray ; DNA ; metabolism ; DNA Cleavage ; Deoxyribonucleases, Type II Site-Specific ; chemistry ; genetics ; metabolism ; Escherichia coli ; metabolism ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Recombinant Proteins ; chemistry ; genetics ; metabolism ; Sequence Alignment ; Substrate Specificity