Peripheral immune profile and gene variations of 11 immunodeficiency virus-negative children with Talaromyces marneffei infection / 中华实用儿科临床杂志

Objective:To explore the immunological characteristics of peripheral blood and genetic variations of 11 immunodeficiency virus(HIV)-negative children with Talaromyces marneffei(TM) infection, thus enhancing the diagnostic and therapeutic levels of TM infection in children. Methods:Clinical data of 11 HIV-negative children with TM infection who presented to Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2010 to December 2022 were retrospectively analyzed, including clinical characteristics, peripheral immune profile and genetic test results.Results:A total of 11 HIV-negative children with TM infections were recruited, involving 9 males and 2 females with a median age of 19 months.The main clinical manifestations were fever (10/11, 90.91%), cough (10/11, 90.91%) and hepatomegaly (7/11, 63.64%). Common severe complications included acute respiratory distress syndrome (7/11, 63.64%) and septic shock (5/11, 45.45%). Finally, 2 children died.Transient neutropenia occurred in 6 cases (6/11, 54.55%), and lymphocytopenia combined with serum immunoglobulin (Ig) G decrease was observed in 4 cases (4/11, 36.36%). IgA decrease, IgM decrease, IgE decrease, IgM increase and IgE increase were observed in 6 cases, 3 cases, 5 cases, 3 cases, and 2 cases, respectively.Both T-lymphocyte and B-lymphocyte counts decreases was observed in 1 case.Genetic testing was performed in all recruited children, and genetic variations were detected in all of them.Inborn errors of immunity (IEIs) were diagnosed in 8 cases, including 4 diagnosed as CD 40 ligand deficiency with CD40LG variation, 1 of severe combined immunodeficiency with IL2RG variation, 1 of Signal transduction and activator of transcription 3(STAT3)-hyper-IgE syndrome with STAT3 variation and 1 of familial candidiasis type 2 with CARD9 compound heterozygous mutations.In the other 3 cases, 2 carried genetic variations that were likely pathogenic, and 1 case was considered uncertain. Conclusions:The clinical manifestations of HIV-negative children with TM infection are atypical, which is characterized as serious complications and high mortality.Early identification and gene testing to detect potential IEIs can improve the prognosis of TM infection.

Analysis of drug resistance gene variation of influenza A（H1N1） pdm09 virus in Huzhou City，Zhejiang Province / 上海预防医学

ObjectiveTo investigate the mutation and genetic evolution of drug resistance gene of A（H1N1） pdm09 influenza pandemic strain in 2023 in Huzhou City， Zhejiang Province. MethodsRespiratory tract specimens from 2 influenza monitoring hospitals were collected forA（H1N1） pdm09 influenza virus nucleic acid detection. Positive specimens were inoculated with MDCK cells for influenza virus isolation and sequencing. DNA Star 7.1 software and Mega 4.0 software were used to analyze the neuraminidase （NA） enzyme active site and the amino acid sites related to drug resistance in M2 protein. ResultsNucleotide homology and amino acid homology of NA between the isolated and the vaccine strains were 98.87%‒99.22% and 98.94%‒99.36%， respectively. The nucleotide homology range of M gene was 99.07% to 99.85%， and the amino acid homology range was 99.02%‒99.94%. The isolates and vaccine strains belong to the evolutionary clades of 6B.1A.5a.2a. The amino acids at the key sites of the enzyme activity center of NA were still highly conserved， and the 9 key amino acid sites related to NA inhibitor resistance did not change， but some mutations occurred at the non-enzyme active sites in some popular strains. The 5 amino acid sites related to drug resistance of M2 protein were not replaced， but the 31st amino acid sites changed from serine to asparagine. ConclusionThe A（H1N1） pdm09 pandemic strain in Huzhou in 2023 has high homology with the 2023‒2024 vaccine strain recommended by WHO. All endemic strains are resistant to amantadines.

A family study of congenital nephrogenic diabetes insipidus combined with hyperuricemia / 中华内分泌代谢杂志

Objective:To investigate the clinical and genetic characteristics, pathogenesis and treatment strategy of congenital nephrogenic diabetes insipidus(CNDI)combined with hyperuricemia.Methods:The clinical manifestations and laboratory data of an infant patient diagnosed as CNDI with hyperuricemia and his family members were collected and retrospectively analyzed. Whole exome sequencing(WES)was applied to detect the proband′s genome variation of each exon and suspected variants of AVPR2 and ABCG2 were verified by PCR-Sanger sequencing of members from his pedigree. Furthermore, we retrospectively collected the serum uric acid levels of patients(≤14-year-old) with CNDI in the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2022.Results:The proband was clinically diagnosed with CNDI and the rest of the family members had no symptoms of polydipsia or polyuria. In addition to the proband, his father was also suffered from hyperuricemia. WES showed that the proband carried a hemizygous AVPR2 gene variation(p.S331R)and a heterozygous ABCG2 gene variation(p.N308K). The former was X-linked recessive inheritance from his mother, and the latter was autosomal dominant inheritance from the father. Fraction excretion of uric acid(FEUA)of the proband and his father with hyperuricemia were 3.1% and 2.7%, respectively. Twelve children(≤14-year-old)were diagnosed with CNDI from the respective study. Among all the cases, 11 patients were male and 1 was female, ranging from 3-month to 14-year-old. Five patients were accompanied with hyperuricemia.Conclusion:Children with CNDI may be complicated with hyperuricemia, and the regimen of hydrochlorothiazide combined with benzbromarone is effective. The pathogenicity of the AVPR2 gene variation(p.S331R)and ABCG2 gene variation(p.N308K)in this pedigree needs to be further studied.

Clinical features of six patients with Neurodevelopmental disorder with spastic diplegia and visual defects caused by CTNNB1 gene mutation / 中华检验医学杂志

Objective:To investigate the clinical features and characteristics of gene mutation of patients with neurodevelopmental disorder caused by CTNNB1 gene. Method:Genetic mutation analysis of the patients were obtained by using the whole exome sequencing and Sanger sequencing. We reviewed the literatures for the clinical and genetic features of CTNNB1 related neurodevelopmental disorder. Results:Six inpatients, three boys and three girls, who came for speech impairment motor delay were included in this study. The average age for the patients was 17.8±11.1 months. The main clinical manifestations of the patients were craniofacial dysmorphism, microcephaly, hypertonia or spasm, speech impairment motor delay, esotropia and valgus. WES showed that 6 patients carried de novo mutations of CTNNB1 gene, which were c.1057delA, c.1493_1494insA, c.418_424del, c.1985_1988del, c.1420C>T and c.1550T>C. No abnormality was found in the patients′ parents. Conclusions:The clinical manifestation of CTNNB1 related neurodevelopmental disorder involves multiple systems. We found five unreported variants and expanded the variation spectrum of the CTNNB1 gene.

Results of neonatal screening for congenital hypothyroidism and hyperphenylalaninemia in Zhejiang province from 1999 to 2022 / 浙江大学学报·医学版

OBJECTIVES@#To analyze the results of neonatal screening for congenital hypothyroidism (CH) and hyperphenylalaninemia (HPA) in Zhejiang province from 1999 to 2022.@*METHODS@#A total of 11 922 318 newborns were screened from September 1999 and December 2022 in Zhejiang province. The blood thyroid stimulating hormone (TSH) levels were measured by a fluorescence method and blood phenylalanine (Phe) levels were measured by fluorescence method or tandem mass spectrometry. TSH≥9 μIU/mL was considered positive for CH, while Phe>120 μmol/L and/or Phe/Tyr ratio>2.0 were considered positive for HPA. The positive newborns in screening were recalled, and the gene variations were detected by high-throughput sequencing and MassARRAY tests.@*RESULTS@#The overall neonatal screening rate during 1999-2022 was 89.41% (11 922 318/13 333 929) and the screening rate was increased from 6.46% in 1999 to 100.0% in 2022. A total of 8924 cases of CH were diagnosed among screened newborns with an incidence rate of 1/1336. A total of 563 cases of HPA were diagnosed, including 508 cases of classic phenylketonuria (cPKU) and 55 cases of tetrahydrobiopterin deficiency (BH4D), with an incidence rate of 1/21 176. Ninety-seven out of 8924 cases of CH underwent genetic analysis. Gene mutations were detected in 9 CH related genes, the highest frequency mutations were found in DUOX2 gene (69.0%) with c.3329G>A (p.R1110Q) (18.2%) and c.1588A>T (p.K530X) (17.3%) as the hotspot mutations. There were 81 PAH gene variants detected in a total of 250 cases of cPKU, and c728G>A (p.R243Q) (24.4%), c.721C>T (p.R241C) (15.0%) were the hotspot mutations. Meanwhile 7 novel variants in PAH gene were detected: c.107C>A (p.S36*), c.137G>T (p.G46V), c.148A>G(p.K50E), c.285C>T (p.I95I), c.843-10delTTCC, exon4-7del and c.1066-2A>G. There were 12 PTS gene variants detected in 36 cases of BH4D, and c.259C>T (p.P87S) (31.9%) was the hotspot mutation.@*CONCLUSIONS@#The incident of CH has increased from 1999 to 2022 in Zhejiang province, and it is higher than that of national and global levels; while the incidence of HPA is similar to the national average. DUOX2 gene variation is the most common in CH patients; c.728G>A (p.R243Q) is the hotspot mutation in cPKU patients, while c.259C>T (p.P87S) is the hotspot mutation in BH4D patients.

Analysis of genotypes and biochemical phenotypes of neonates with abnormal metabolism of butyrylcarnitine / 浙江大学学报·医学版

OBJECTIVES@#To investigate the genotypes and biochemical phenotypes of neonates with abnormal metabolism of butyrylcarnitine (C4).@*METHODS@#One hundred and twenty neonates with increased C4 levels detected by tandem mass spectrometry in the neonatal screening at Children's Hospital, Zhejiang University School of Medicine from January 2018 to June 2023 were included. The initial screening data and recalled data of C4 and C4/C3 were collected and converted into multiples of C4 reference range. Next generation sequencing was performed and the exons with adjacent 50 bp regions of ACAD8 and ACADS genes were captured by liquid phase capture technique. Variant information was obtained by bioinformatic analysis and the pathogenicity were classified according to the American College of Medical Genetics and Genomics criteria. The Wilcoxon rank sum test was used to analyze the differences in C4 levels among neonates with different variation types.@*RESULTS@#In total, 32 variants in ACAD8 gene were detected, of which 7 variants were reported for the first time; while 41 variants of ACADS gene were detected, of which 17 variants have not been previously reported. There were 39 cases with ACAD8 biallelic variations and 3 cases with ACAD8 monoallelic variations; 34 cases with ACADS biallelic variations and 36 cases with ACADS monoallelic variations. Furthermore, 5 cases were detected with both ACAD8 and ACADS gene variations. Inter group comparison showed that the multiples of C4 reference range in initial screening and re-examination of the ACAD8 biallelic variations and ACADS biallelic variations groups were significantly higher than those of the ACADS monoallelic variations group (all P<0.01), while the multiples in the ACAD8 biallelic variations group were significantly higher than those in the ACADS biallelic variations group (all P<0.01). The multiples of C4 reference range in the initial screening greater than 1.5 times were observed in all neonates carrying ACAD8 or ACADS biallelic variations, while only 25% (9/36) in neonates carrying ACADS monoallelic variations.@*CONCLUSIONS@#ACAD8 and/or ACADS gene variants are the main genetic causes for elevated C4 in newborns in Zhejiang region with high genotypic heterogeneity. The C4 levels of neonates with biallelic variations are significantly higher than those of neonates with monoallelic variations. The cut-off value for C4 level could be modestly elevated, which could reduce the false positive rate in tandem mass spectrometry neonatal screening.

Genetic variation analysis of Human Papillomavirus 16 E4 and L2 in women with cervical infection in Xinjiang Uygur Autonomous Region / 安徽医科大学学报

Objective @#To explore the nucleotide variation and protein amino acid changes of E4 and L2 genes of Human Papillomavirus 16 (HPV16) , and to analyze the evolutionary characteristics of HPV16 virus.@*Methods @# 40 HPV16 infection⁃positive cervical exfoliated cells samples and tissue cell samples were collected from hospital , viral DNA was extracted , Sanger sequencing perform in cervical exfoliated cells DNA and high⁃throughput sequencing technology sequenced in cervical tissues DNA for E4 and L2 genes of HPV16 , HPV16 E4 and L2 gene phylogenetic evolution trees were constructed , and variation of HPV16 E4 and L2 genes were analyzed. @*Results @#There were 72 HPV16 E4 variant samples with nucleotide variants (4 missense mutations and 7 synonymous mutations) at 10 sites , HPV16 L2 gene variants in 74 samples , and nucleotide variants (23 missense mutations and 18 synonymous mutations) at 40 sites. The variation frequency of T4177C , A4288C and A4654C in cervical cancer was significantly higher than that in non⁃cervical cancer, and the difference was statistically significant (P < 0. 05) . @*Conclusion@#① The main HPV16 virus strains in Xinjiang are European strains , and a few are Asian strains. ② The mutation frequency of T4177C , A4288C and A4654C in HPV16 L2 gene is higher than that in non⁃cervical cancer, and G4181A is related to the Asian strain.

Genetic analysis of neonates with abnormal isovaleryl carnitine metabolism / 中华实用儿科临床杂志

Objective:To explore the genetic causes of abnormal isovaleryl carnitine (C5) metabolism in newborns.Methods:Retrospective study.The screening and clinical follow-up data of 34 neonates with elevated C5 levels shown by the tandem mass spectrometry test in Children′s Hospital, Zhejiang University School of Medicine from January 2018 to December 2021 were collected.Afterwards, their ethylenediaminetetraacetic acid (EDTA) anticoagulant venous blood was collected to extract genomic DNA.A total of 79 genes related to genetic metabolic diseases, such as ACADSB, IVD and ACADM, were captured by liquid-phase capture technology.High-throughput sequencing and bioinformatics analysis were used to acquire gene variation information and the genes were categorized by American College of Medical Genetics and Genomics classification standard.According to the results of genetic analysis, the newborns with C5 elevation were divided into 3 groups: non-mutation group(11 cases), ACADSB mutation group(16 cases) and IVD mutation group(7 cases). Wilcoxon rank sum test was performed to analyze the difference between these groups. Results:Among 34 neonates, 6 ACADSB variants were detected in 16 cases, and 2 of them [c.461G>A (p.G154E), c.746delC(p.P249Lfs*15)] were novel variants.Eleven IVD variants were detected in 7 cases, and 7 of them [c.118A>G(p.N40D), c.296-10C>G, c.302A>G(p.Y101C), c.537G>A(p.M179I), c.667C>T(p.R223W), c.983A>G(p.K328R), c.1147+ 5G>A] were never reported before.There was no significant difference in the C5 concentration in initial screening among the three groups ( P>0.05). Conclusions:Mutations in ACADSB and IVD genes are the main causes of augmented C5 levels in neonatal screening.For newly discovered genetic variants, functional prediction by multiple bioinformatics analysis software is recommended.And it is also important to carry out clinical follow-up and evaluation.

Clinical analysis of 36 cases of neonatal-onset genetic epilepsy / 中国新生儿科杂志

Objective:To study the genetic profiles and clinical characteristics of neonatal-onset genetic epilepsy.Methods:From July 2016 to May 2021, patients with neonatal-onset genetic epilepsy admitted to our hospital and received second-generation genetic sequencing were enrolled in this study. According to the types of genetic variations, the patients were assigned into ion channel group and non-ion channel group. Clinical characteristics, treatments and prognosis of the two groups were compared.Results:A total of 36 patients with identified genetic variations were enrolled, involving 15 epilepsy-related genes. KCNQ2, SCN2A and STXBP1 were the most common pathogenic genes. 20 cases (55.6%) were in the ion channel group and 16 cases (44.4%) in the non-ion channel group. No significant differences existed in their general status, seizure types, EEG characteristics, treatments and outcomes between the two groups ( P>0.05). Among all 36 cases, the age of onset ranged from 10 min to 24 d after birth and 28 cases (78.8%) developed epilepsy within 1 week after birth. Developmental and epileptic encephalopathies were diagnosed in 20 patients. 7 patients were diagnosed with self-limited neonatal epilepsy, 2 were pyridoxine dependence, 2 were Zellweger syndrome and 1 case of self-limited familial neonatal-infantile epilepsy, Turner type mental retardation with epilepsy, PURA syndrome, Rett syndrome and 22q11.2 deletion syndrome, each. The patients received antiepileptic drugs including phenobarbital, levetiracetam, oxcarbazepine, topiramate, valproic acid, benzodiazepines (nizepam/clonazepam /clobazam/midazolam), lacosamide and lamotrigine. 5 patients died after giving up treatment. 31 patients were followed up for 6 to 50 months. 22 cases (71.0%) were controlled at 1- to 35-month-old including 21 cases (56.7%) with developmental delay. 6 cases (19.4%) had ineffective seizure control and 3 cases (9.7%) showed reduced seizures, all with varying degrees of developmental delay. Conclusions:Neonatal-onset epilepsy is correlated with multiple genes. KCNQ2, SCN2A, STXBP1 are the common pathogenic genes with multiple variants of KCNQ2 gene. Most patients have seizures within 1 week after birth. More than half of patients have ion channel related gene variations. Sodium channel blockers have certain effects as treatment.

Study on genetic etiology of two cases with hypophosphatasia(HPP) using whole-exome sequencing / 中华内分泌代谢杂志

Objective:Clinical and genetic analysis were conducted in 2 patients with hypophosphatasia(HPP) and their families to explore the pathogenic mechanism of HPP.Methods:The genomic DNA was extracted from peripheral blood of two patients with HPP and their family members. Sanger sequencing and pedigree verification were performed on the pathogenic variants identified using whole-exome sequencing. Then the function of the mutation sites was analyzed with bioinformatics software.Results:Proband 1 presented with developmental retardation, pectus funnel and premature loss of deciduous tooth, of which the serum alkaline phosphatase level was slightly lower than the bound of the normal range. Two complex heterozygous missense variants c. 1120G>A and c. 1334C>G of ALPL gene were detected in the proband 1 which were inherited from his parents respectively, showing an autosomal recessive inheritance. Both the variants were predicted to inflict deleterious effects on ALPL gene function by multiple bioinformatics program, and were classified as likely pathogenetic variants according to American College of Medical Genetics and Genomics(ACMG) guidelines. Proband 2 showed three missing permanent teeth and the significantly lower level of serum alkaline phosphatase than normal range. A heterozygous variant c. 1190-3C>G of ALPL gene was detected in proband 2 whose pattern of inheritance was unknown. The clinical significance of this variant was unknown according to ACMG standards and guidelines. All of these variants were considered as novel since none of them has been reported. Along with the above combined results, proband 1 and 2 were diagnosed as childhood HPP and Odontohypophosphatasia, respectively.Conclusion:This study reinforced the relationship between HPP and variants in ALPL gene. Two variants, c. 1120G>A and c. 1334C>G, were located in the homodimer interface and crown domain of tissue-nonspecific alkaline phosphatase(TNSALP), respectively, while c. 1190-3C>G were located in the splice sites, which might result in low TNSALP activity.

Clinical features, genetic variations and enzyme replacement therapy in five Chinese patients with Fabry disease / 中华肾脏病杂志

Objective:To analyze the efficacy and safety of enzyme replacement therapy (ERT) in Chinese patients with Fabry disease.Methods:A retrospective analysis of the clinical manifestations, genetic variations, family screening, treatments and adverse reactions was conducted in five patients with Fabry disease admitted to the First Affiliated Hospital of Zhejiang University College of Medicine from July 2020 to May 2021. The dosage of agalsidase β was 1 mg/kg by intravenous pump once every 2 weeks.Results:Five male patients with median age of 37 years old (29-51 years old) were diagnosed based on clinical features, family history, α-galactosidase A (α-Gal A) activity, genetic analysis results and kidney biopsy. The clinical manifestations varied in these five patients. All patients had abnormal electrocardiogram, abnormal cardiac ultrasonography and abnormal urinalysis results, three experienced acroparaesthesia during childhood (one patient had persistent pain until adulthood), three had cutaneous angiokeratoma, four had renal insufficiency, four had hypohidrosis, four had diarrheas, four had cornea verticillata and two had high-frequency hearing loss. Two missense mutations of the GLA gene were identified: c.272T>C(p.I91T) and c.868A>G(p.Met290Val). Two nonsense mutations were c.1024C>T(p.Arg342*) and c.838C>T(p.Gln280*). Furthermore, the frameshift mutation c.348del p.(Ile117Phefs*4) was detected, which was not included in the known database, presented with classical Fabry disease. There was no serious adverse reaction during agalsidase β infusion in 5 patients. ERT reduced the plasma globotriaosylsphingosine (lyso-GL-3) levels after treatment of 2-10 months ( P<0.05), and the long-term diarrhea symptom were significantly improved. Conclusions:The clinical manifestations of Fabry disease are varied. Severe adverse events rarely occur in patients treated with short-term ERT. Plasma lyso-GL-3 levels decrease significantly after treatment.

Progress of hereditary thrombocytopenia in children / 国际儿科学杂志

Hereditary thrombocytopenia(HT)is a hemorrhagic disease characterized by thrombocytopenia caused by genetic variation.HT can be manifested as simple thrombocytopenia or combined syndrome, and its clinical manifestations are complex.It often occurs in children.The unique clinical characteristics of HT are platelet dysfunction, unstable course of the disease and susceptibility to other diseases.Due to different pathogenic genes, the treatment and prognosis of HT are diverse.The evaluation of hemorrhage in the clinical management of HT children is very important.In addition, platelet transfusion, thrombopoietin receptor agonists, hematopoietic stem cell transplantation and gene therapy also supply new ideas for HT treatment.This review summarized the current research progress on HT, in order to help clinicians comprehensively identify HT and take active and effective treatment programs.

Correlation of Leptin Receptor Gene Variation with Blood Pressure and Glucose Level in Type 2 Diabetes Mellitus Subjects of Ternate Population, East of Indonesia

@#Introduction: The leptin receptor gene (LEPR) variation plays an important role in diseases related with obesity which include Type 2 Diabetes Mellitus (T2DM) and hypertension in some populations. The role of this variation is still controversial and not yet studied in the eastern parts of Indonesia. Hence, this study aimed to explore the correlation of leptin receptor variations (Lys109Arg and Gln223Arg) with blood pressure and blood glucose in T2DM in Ternate population. Methods: This study examined 136 subjects with the age range of 32-76 years old. Five mL of fasting blood were taken to determine blood glucose levels using the GOD-PAP method, and leukocytes were used for genotyping by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique methods. Frequencies of genotypes and alleles were analyzed with chi square tests. Correlations of genotypes with the anthropometric measurements were calculated by logistic regression with significance value if p<0.05. Results: Variation of Lys109Arg LEPR gene did not influence the Body Mass Index (BMI), blood pressure, nor blood glucose level. Variation of Gln223Arg LEPR gene also did not influence BMI and blood glucose level, but correlated with blood pressure. Regression analysis after adjusted for age, gender, BMI and blood glucose level showed that this variation remains significantly different. Conclusion: Variation of Gln223Arg LEPR gene correlated with blood pressure but variation of Lys109Arg LEPR gene was not correlated with blood glucose level nor blood pressure. Future study is needed to correlate other genes and examine their effect on metabolic syndrome diseases.

Application of gene variation detection technology in precision medicine of malignant cancers / 中国肿瘤生物治疗杂志

@# Malignant cancer is a kind of fatal disease with severe threat to human health and social development, and seeking a scientific method for the proper diagnosis, treatment and assessment has become one of the most important public health problems in recent years. With the constant development in healthcare industry, traditional methods of tumor screening, prevention and prognosis assessment have made a rapid progress. However, owing to the characteristics of tumor heterogeneity and patient individuation, precision medicine mode in disease screening, diagnosis and treatment will become a general trend in future medical development. As an important part in precision medicine, gene variation detection in the field of tumors involves several aspects, including early screening, recurrence monitoring, guidance on use of targeted drugs and assessment of efficacy and prognosis etc; However, there are still many limitations in its clinical practice. Therefore, further research is needed to promote the development of tumor precision medicine. In this paper, the development history of gene variation detection and its application progress in precision medicine of malignant tumors are comprehensively discussed.

Tricho-rhino-phalangeal syndrome due to a novel frameshift variation of the TRPS1 gene / 中华医学遗传学杂志

Objective@#To explore the genetic etiology of a pedigree affected with tricho-rhino-phalangeal syndrome.@*Methods@#Next-generation sequencing (NGS) using a gene panel for hereditary osteopathies was carried out for the proband. Suspected mutation was validated in the proband and her parents by Sanger sequencing.@*Results@#A heterozygous frameshift variation c. 1995dupA (p.Gly666Argfs*20) of the TRPS1 gene was detected in the proband but not in her parents.@*Conclusions@#The novel c. 1995dupA (p.Gly666Argfs*20) mutation of the TRPS1 gene probably underlies the disease in the proband.

Genotype and evolution of hantavirus in Tiantai of Zhejiang province, 2011-2018 / 中华流行病学杂志

Objective@#By investigating the genotype and evolutionary variation of hantavirus (HV) in Tiantai county, a national surveillance site for hemorrhagic fever with renal syndrome (HFRS) was set in Zhejiang province, from 2011 to 2018, to reveal the molecular epidemiological characteristics of hantavirus (HV) in Tiantai.@*Methods@#Total RNA was extracted from ultrasound treated HV antigen- positive rat lung samples in Tiantai from 2011 to 2018. After cDNA was prepared, nested PCR was used to amplify partial sequence of M fragments by using specific primers of HV. The sequences of HV in Tiantai from 2011 to 2018 were compared with other known HV sequences in order to identify the genotype and analyze the evolution and variation of the virus.@*Results@#In 67 HV antigen-positive lung specimens, 31 were positive in nested PCR amplification with type-specific primers, including 30 Hantaan virus (HTNV) positive samples, 1 Seoul virus (SEOV) positive sample, and all the 31 samples were from Apodemus agrarius. The phylogenetic tree based on partial M segment was divided into monophyletic group, 30 strains were distributed in HTNV group and 1 was in SEOV group. The HTNV strain Tiantai T2018-130 was independently in one branch, sharing 84.8%-87.9% homology with other strains both at home and abroad, including 29 strains in HTNV group in Tiantai. The other 29 HTNV strains in Tiantai showed closer relationship. The SEOV strain T2016-31 from Apodemus agrarius showed closer relationship with previous strains of SEOV, Tiantai ZT71, ZT10 and Z37 strains of Wenzhou, Zhejiang province.@*Conclusions@#HTNV, the main genotype of HV in Tiantai of Zhejiang province, showed obvious geographic clustering, but the strain T2018-130 was distinct from the others in Tiantai. Meanwhile, by sequence analysis, we confirmed that The SEOV strain T2016-31 existed in in Apodemus agrarius, indicating there was a phenomenon of "spillover" between virus and host in SEOV evolution.

Analysis of P gene variations among fourteen patients with oculocutaneous albinism type Ⅱ / 中华医学遗传学杂志

Objective@#To analyze variations of TYR and P genes among 14 patients with clinically diagnosed oculocutaneous albinism.@*Methods@#Potential variations of the TYR and P genes were detected by Sanger sequencing. Novel variations were predicted with bioinformatics software including SIFT and PolyPhen-2.@*Results@#No variation was found in the TYR gene, while 9 types of variations were found in the P gene among the 14 patients, which included c. 803-3C>G (7/26), c. 1327G>A (p.Val443Ile) (5/26), c. 632C>T (p.Pro211Leu) (4/26), c. 1832T>C (p.Leu611Pro) (3/26), c. 1349C>A (p.Thr450Lys) (2/26), c. 2363C>T (p.Ser788Leu) (2/26), c. 2228C>T (p.Pro743Leu) (1/26), c. 1525A>G(p.Thr509Ala) (1/26), and c. 1349C>T(p.Thr450Met) (1/26). Only 1 heterozygous variation was detected in 2 families. c. 2363C>T (p.Ser788Leu), c. 1832T>C (p.Leu611Pro) and c. 1525A>G (p.Thr509Ala) were not reported previously and predicted as "harmful" to the protein function.@*Conclusion@#The main type of ocular albinism is oculocutaneous albinism type Ⅱ in Liuzhou region, where the most common variations of the P gene were c. 803-3C>G and c. 1327G>A (p.Val443Ile). Above finding has enriched the variation spectrum of the P gene.

Emerging alveolar echinococcosis and gene fragments of Nad 2 and Cob in Nileke County, Yili area of Xinjiang, China / 中国人兽共患病学报

We investigated the endemic situation of alveolar echinococcosis (AE) in Nileke County,Yili Prefecture,Xinjiang and its genetic diversity of Echinococcus multilocularis.Human AE cases in the county were retrospectively investigated including their location and surrounding ecological conditions.Sequence detection and analysis of nad2,cob gene fragments of AE mtDNA from patients was used to identify genotype variation.Results showed that a total of 48 AE cases were diagnosed and the first AE patient was identified in 1989 in the county.The 45.8％ of AE cases were found in the recent 5 years (2011-2015) and annual prevalence was 1.7 per 100 000.The patients were distributed along the Kashgar River,particularly intensive in Wulasitai Township.The 38.6％ of the patients were aged arranged 35-44 years old,64.6％ were male and 95.8％ were farmers and herdsmen.AE cases were confirmed further and there was only one haplotype by sequencing analysis from 11 AE clinical patients in the county.It suggests that Nileke County is AE foci,and alveolar echinococcosis with sequences conserved is an emerging disease in the county.

Gene regulatory network of hepatocellular carcinoma: a review / 生物工程学报

Hepatocellular carcinoma (HCC) is one of the common malignant tumors. HCC gene regulatory network (HCC GRN), whose nodes consist of genes, miRNAs or TFs and whose edges consist of interaction relationships of nodes, is one of the important ways to study molecular mechanism of HCC. Based on various experimental data, types of HCC GRNs could be conducted such as TF-miRNA regulatory network. Integrating the studies of HCC GRN, TF-miRNA transcriptional regulatory network performs better in identifying core genes which play important roles in network disturbances. It is a trend that gene variations and transcriptional regulatory networks should be combined, however the corresponding research is almost blank. This review summarizes the source of HCC data sources, the classification, character, and research program of HCC GRN. Finally, according to present analysis and discussion of progress and research status of HCC GRN, we provide a useful reference for researchers.

Identification of Anaplasma specise in some anima sl from Xitianmu Mountain in Zh ejiang province / 中华微生物学和免疫学杂志

Objective To identify Anaplasma species circulating among livestock and rodents from Xitianmu Mountain area in Zhejiang province , Southeastern China and to analyze variations regarding to their 16S rRNA gene.Methods Samples of spleen, liver and blood were collected to extract DNAs .The 16S rRNA gene fragments of Anaplasma species were amplified by using a nested PCR and then sequenced .Ho-mology analysis was conducted by using BLAST program .The multiple sequence alignment and phylogenetic analyses comparing with the sequences of other Anaplasma species in GenBank were conducted by using MEGA 5.0 software.Results The 16S rRNA gene fragments of Anaplasma were detected in 1 cattle, 8 goats, 5 Rattus confucianus, 1 Apodemus agrarius, 1 Berylmys bowersi and 1 squirrel out of 129 animals. The natural infection rate of Anaplasma was 13.2% in animals from Xitianmu Mountain area in Zhejiang . The alignment and phylogenetic analyses indicated that there were at least four Anaplasma species prevalent in livestock and rodents from Xitianmu Mountain area , including Anaplasma phagocytophilum, Anaplasma marginale, Anaplasma centrale and Anaplasma bovis.Moreover, there was a variant that obviously differed from Anaplasmma bovis and other Anaplasma sp.in GenBank.Conclusion The Anaplasma infection was detected among livestock and rodents from Xitianmu Mountain area in Zhejiang province .A newly discovered variant in rodents was likely to be a novel species .More close attention should be paid to Anaplasma infec-tion among human in Xitianmu Mountain area .