Objective:To investigate the clinical and genetic features of the patient with neurodevelopmental disorders characterized by thickened corpus callosum caused by MAST1 gene mutation. Methods:Clinical data and auxiliary examination of a child with neurodevelopmental disorders caused by MAST1 gene mutation who was admitted to Henan Children′s Hospital in September 2022 were collected, and whole exome sequencing technology was applied to analyze the genetics of the child. Results:The patient was a 2 years and 8 months old male, with a clinical phenotype including intellectual, motor, and speech development disorders. Brain magnetic resonance imaging (MRI) showed thickened corpus callosum, nodular heterotopia of the left ventricle body.Whole exome sequencing showed the MAST1 gene with c.578T>G(p.Met193Arg) heterozygous missense variant, which was a unreported de novo pathogenic variant and both of his parents were wild-type. Conclusions:Diseases caused by MAST1 gene mutations are relatively rare, the main clinical features are neurodevelopmental disorders and brain structural abnormalities, and MRI shows an enlarged corpus callosum.The heterozygous missense variant c.578T>G(p.Met193Arg) of the MAST1 gene is the genetic cause of this case.

The pollution caused by improper handling of plastics has become a global challenge. In addition to recycling plastics and using biodegradable plastics, an alternative solution is to seek efficient methods for degrading plastics. Among them, the methods of using biodegradable enzymes or microorganisms to treat plastics have attracted increasing attention because of its advantages of mild conditions and no secondary environmental pollution. Developing highly efficient depolymerizing microorganisms/enzymes is the core for plastics biodegradation. However, the current analysis and detection methods cannot meet the requirements for screening efficient plastics biodegraders. It is thus of great significance to develop rapid and accurate analysis methods for screening biodegraders and evaluating biodegradation efficiency. This review summarizes the recent application of various commonly used analytical techniques in plastics biodegradation, including high performance liquid chromatography, infrared spectroscopy, gel permeation chromatography, and determination of zone of clearance, with fluorescence analysis techniques highlighted. This review may facilitate standardizing the characterization and analysis of plastics biodegradation process and developing more efficient methods for screening plastics biodegraders.
Biodegradable Plastics/chemistry* ; Biodegradation, Environmental

Objective:To analyze the clinical characteristics and genetic variation of 2 children with developmental and epileptic encephalopathy 8 (DEE8).Methods:Whole-exome sequencing (WES) was performed to determine the potential variants in the probands. Candidate variants identified by WES were validated by Sanger sequencing and quantitative real-time polymerase chain reaction. X chromosome inactivation (XCI) detection was performed in the proband 1′s mother and proband 2 to detect the allelic expression difference of ARHGEF9. Results:Both of the cases showed global developmental delay. Proband 1 presented with delayed motor and speech development, intellectual disability, and seizures. Electroencephalography of proband 1 showed slow background activity, with spikes, spike and waves in bilateral frontal and midline regions during sleep. While proband 2 showed delay in acquisition of language, motor skills, and cognition, but no seizures. It was identified that proband 1 carried a novel maternally derived heterozygous splicing variant (c.925-2A>T) in ARHGEF9 by WES, which was verified in Sanger sequencing. The XCI in proband 1′s mother was observed, and the expression ratio of mutant ARHGEF9 and wild-type was 0∶100%. A novel exon 3-10 heterozygous deletion of ARHGEF9 was identified in proband 2, and this variant was not found in his unaffected parents. Conclusions:DEE8 disorders are relatively rare. Most of the patients have varying degrees of neurodevelopmental phenotype, but epilepsy is not a specific clinical manifestation. ARHGEF9 gene deletion and splicing variation may be the genetic cause of the 2 probands, and above findings have enriched the spectrum of variation and phenotype of DEE8.

Objective:To analyze the clinical characteristics of children aged two years old and above with respiratory syncytial virus (RSV) infection in pediatric intensive care unit (PICU).Methods:Children who had RSV infection admitted to PICU at Children′s Hospital of Zhengzhou University from March 2019 to December 2021 were divided into older age group(≥two years old) and younger age group(0.05); In younger age group, there were 132(64.8%) cases of fever and 125(64.8%) cases of wheezing; In older age group, there were 31(93.9%) cases of fever and 13(39.4%) cases of wheezing; the incidence of fever was higher in older age group than that in younger age group( χ2=9.147, P<0.05), and the incidence of wheezing was lower than that in younger age group( χ2=7.631, P<0.05), and the differences were statistically significant.(2) There were 15 (45.5%) cases of simple infection and 18 (54.5%) cases of mixed infection in older age group, and the P/F was significantly different between children with simple infection and those with mixed infection ( P<0.05); there were 14 (42.4%) cases of combined underlying diseases and 19 (57.6%) cases without underlying diseases, and the length of stay in PICU was different between children with combined underlying diseases and those without underlying diseases ( P<0.05), and there was no significant difference in mechanical ventilation or total length of stay ( P>0.05). Conclusion:RSV infection in children aged two years old and above in PICU occurres mostly between two and six years of age, with a relatively low incidence of wheezing and common fever; RSV infection alone may have a greater impact on oxygenation, and combined underlying diseases can affect the length of stay in PICU.

Objective:To explore the value of immediate bedside blood culture in the adjustment of antibiotics for children with bloodstream infections in pediatric intensive care units(PICU).Methods:Retrospective analysis of children in PICU at Henan Children′s Hospital from May 2017 to March 2021 was conducted.The cases were divided into laboratory blood culture(LBC) group and satellite blood culture(SBC) group according to different blood culture methods.The difference in the time to blood culture incubation, time to blood culture positivity, microbial results time and antibiotic adjustment time were compared between two groups.Results:A total of 3 720 blood cultures were completed in 2 718 children, including 1 888 in LBC group and 1 832 in SBC group, with a positive rate of 3.5% in LBC group and 4.9% in SBC group, and a significantly higher positive rate in SBC group compared to LBC group( χ2=3.954, P=0.046). The differences in age, sex, site of infection, survival rate at 28 d after discharge, pediatric critical illness score, and pediatric risk of mortality Ⅲ score between LBC group and SBC group with positive blood cultures were not statistically significant ( P>0.05). Children in SBC group had significantly shorter specimen receipt time, time to obtain microbiological results, and antibiotic adjustment time than those in LBC group[0.33(0.03, 1.78) h vs. 3.38(1.38, 7.29) h, (57.40±21.92) h vs. (68.14±21.26) h, and (52.53±27.23) h vs. (66.41±28.57) h, all P<0.05]. Conclusion:Immediate bedside blood culture shortens the time from culture to final result reporting, increases the positive rate of blood culture, and saves time on accurate antibiotic treatment for critically ill children.

Objective:To summarize the clinical phenotype and genotypic characteristics of children with truncation variation in SMC1A gene. Methods:The clinical data of a child with late-onset cluster seizures caused by truncation variation in SMC1A gene diagnosed in February 2021 in Children′s Hospital Affiliated to Zhengzhou University were collected. The relevant literature was reviewed to summarize the clinical characteristics. Results:The proband was a 5-year-old girl, presenting with first seizure at the age of 5 and cluster seizures. She had poor response to multiple antiepileptic drugs, and had normal neurodevelopment before seizures. Whole exome sequencing results revealed a spontaneous heterozygous nonsense variation c.55C>T in SMC1A gene, causing a nonsense variant in the amino acid sequence p.Gln19Ter(p.Gln19 *), which has not been reported. There were a total of 14 relevant literatures, and there were in total 32 cases with truncation variation in SMC1A gene including this case. All children were female and 30 children had early-onset intractable epilepsy, and first seizure median age was 5 months (range: 4 weeks to 40 months); 78.1% (25/32) of them had cluster seizures; 93.8% (30/32) had mental retardation; Cornelia de Lange syndrome clinical score in 68.8% (22/32) of them was≥4. The truncation variations in SMC1A gene of 31 children were de novo, and there were 16 children with frameshift variation (16/32), 12 children with nonsense variation [12/32; 3 children (9.4%, 3/32) with c.2923C>T], 4 children with splice variation (4/32). Conclusions:This study further expands the clinical phenotype and genotype of cases with truncation variation in SMC1A gene. Case presenting with female late-onset cluster seizures has not been reported in China, and genetic testing can be beneficial for early diagnosis of hereditary epilepsy and precision treatment.

Objective:To investigate the clinical phenotype and gene variation conditions in neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), so as to provide a basis for genetic counseling and clinical diagnosis and treatment of the family.Methods:11 cases of neonatal intrahepatic cholestasis who visited the Children's Hospital Affiliated to Zhengzhou University between February 2019 and March 2021 were selected as the study subjects. High-throughput sequencing technology was used to detect the gene variation condition in 11 neonatal patients and 100 normal control neonates. The suspicious loci and family members were verified by Sanger sequencing and QPCR technology.Results:All 11 children with NICCD had different degrees of jaundice and liver damage symptoms, combined with coagulation dysfunction and anemia ( n = 7), cardiac malformation ( n = 2), elevated myocardial enzymes ( n = 4), hyperlipidemia ( n = 1), hyperkalemia ( n = 1), persistent diarrhea ( n = 3), developmental delay ( n = 1). A total of 10 different types of SLC25A13 gene mutations were detected in 11 cases, including three frameshift mutations, two splicing changes, two missense mutations, one intron insertion, one nonsense mutation, and one heterozygous deletion. After reviewing literature and databases, c.1878delG(p.I627Sfs*73) and exon11 deletion were novel mutations that had not been reported at home or abroad. Conclusion:The clinical features of NICCD are non-specific, and genetic testing aids in the early and accurate diagnosis of the disease, providing an important basis for clinical treatment and genetic counseling for family members. In addition, the detection of novel mutation sites has enriched the SLC25A13 gene variation spectrum.

Objective:To investigate the clinical phenotype and genotype of a male case of subcortical band heterotopia caused by mosaic mutation of DCX gene.Methods:The clinical data and magnetic resonance imaging (MRI) features of a male case of subcortical band heterotopia diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in August 2020 were analyzed retrospectively. At the same time, the whole exon sequencing of the families was performed by next generation sequencing method, the suspicious mutation was verified by polymerase chain reaction Sanger sequencing, and their genetic mutation characteristics were analyzed.Results:The proband, one male, aged 5 years and 1 month, was hospitalized in August 2020 with the complaint of intermittent convulsions for 4 years and six months. Clinical features included that limb muscle tension was slightly high, intellectual and motor development was backward, and head circumference was 48 cm. MRI of his head showed diffuse thick subcortical band heterotopia. The detection of whole exon sequencing in his family showed that there was hemizygous mosaic mutation in DCX gene (mosaic ratio 44%), c.148A>G (p.k50E). The mosaic ratios of oral mucosa and urinalysis were 38.2% and 44.8% respectively. His parents were wild-type, The mutation found in this patient has not been reported at home and abroad.Conclusions:The mosaic variation of DCX gene can cause subcortical band heterotopia in males. The variation of DCX gene c.148A>G (p.k50E) may be the possible cause of the proband, which expands the variation spectrum of subcortical band heterotopia.

OBJECTIVE: To analyze the clinical characteristics and pathogenic gene in a Chinese pedigree affected with mitochondrial DNA depletion syndrome 8A (MTDPS8A). METHODS: Whole exome sequencing was carried out for the patient. Sanger sequencing was used to verify the results, and PolyPhen-2 and PROVEAN software were used to predict the impact of amino acid changes on the function of the protein. RESULTS: The patient, a two-month-old female, was admitted to the hospital for poor milk intake and poor mental response. Her clinical manifestations included feeding difficulty, shortness of breath and low muscle tone. Auxiliary laboratory test indicated that the infant was underdeveloped with abnormal liver, kidney, and heart functions accompanied by hyperlacticacidemia. She responded poorly to treatment and eventually died. Sequencing revealed that the child has carried compound heterozygous missense variants of the RRM2B gene, namely c.16delA (p.R6Gfs*22) and c.175G>C (p.A59P), which were respectively inherited from her father and mother, and both were newly discovered pathologic variants. CONCLUSION The c.16delA and c.175G>C compound heterozygous variants of the RRM2B gene probably underlay the pathogenesis of MTDPS8A. Above finding has strengthened the understanding of the clinical feature and genetic etiology of this disease and expanded the mutation spectrum of the RRM2B gene.
Cell Cycle Proteins ; Child ; China ; DNA, Mitochondrial/genetics* ; Female ; Genetic Testing ; Humans ; Infant ; Mutation ; Pedigree ; Ribonucleotide Reductases ; Whole Exome Sequencing

OBJECTIVE: To conduct clinical and genetic analysis of two male patients with atypical Rett syndrome. METHODS: Collection of clinical data in the two patients and these parents; whole exome sequencing (WES) was used to detect the potential variants, which were verified by Sanger sequencing. X chromosome inactivation (XCI) detection is performed in the Patient 1's mother to detect the allelic expression difference of the MECP2 gene. RESULTS: Patient 1, a 5-year and 10-month-old boy, had mental disorders and mild intellectual disability (ID) (IQ: 54), whose mother had ID. Patient 2 was a 9-month and 18-day-old male presented with recurrent infections, respiratory insufficiency, hypotonia and global developmental delay. WES indentified a hemizygous mutation, c.499C>T (p.R167W), in the MECP2 gene in patient 1, which was inherited from his mother. The inactivation of X chromosome is skewed, and the expression ratio of wild-type and mutant MECP2 is 100%:0. Patient 2 was found a de novo splicing mutation, c.62+2_62+3del in the MECP2 gene. They were both reported pathogenic variant related to Rett syndrome. c.499C>T (p.R167W) was defined as likely pathogenic (PS1+PM2+PP3) and c.62+2_62+3del was pathogenic (PVS1+PM2+PM6) based on American College of Medical Genetics and Genomics standards and guidelines. CONCLUSION Both the two patients were diagnosed with rare male Rett syndrome, which had atypical clinical manifestations and large difference. Above foundings have revealed novel phenotypes in Chinese male patients with Rett syndrome.
Craniosynostoses ; Female ; Genetic Testing ; Humans ; Intellectual Disability/genetics* ; Male ; Methyl-CpG-Binding Protein 2/genetics* ; Mutation ; Phenotype ; Rett Syndrome/genetics*