An inbred strain of DXB/c mouse has been established by hybridization between DBA/2 female mice and C57BL/6 male ones and subsequently by sibmating their offsprings beginning from the F2 generation.Now DXB/c mouse has been passed for 28 generations of full sibmating since 1979.Genetic checkup by means of skin grafting,mandibular morphology analysis,mixed lymphocyte cultivation,coat colour gene testing,and biochemical marker gene examination confirmed that the full homozygosity of alleles has been achieved in DXB/c mouse and DXB/c mouse comforms to the criteria of an inbred strain of mouse.In addition,the genetic background of DXB/c mouse is composed of the genes of its progenitors DBA/2 and C57BL/6 as shown by coat colour gene testing and biochemical marker gene examination.

Objective To investigate the potential effect of Lactobacillus acidophilus (L. acidophilus) on prevention and treatment of neonatal mice infected with human rotavirus (HRV). Methods Sixty 4-day-old kunming mice were randomly divided into control group. HRV infected group, L. acidophilus pretreated group (treated before HRV infection ) and L. acidophilus treated group(treated after HRV infection). The manifestation and pathological changes in small intestine of neonatal mice were observed. The HRV antigen in the feces and intestines were measured by ELISA and fluorescent-focus assay, respectively. Results The severity and duration of diarrhea as well as mortality in L. acidophilus pretreated group and treated group were lower than those in HRV infected group. The duration of HRV-antigens shedding following infection was considerably prolonged in HRV infected group compared to that in L. acidophilus pretreated group and treated group. Furthermore, decreased expression of HRV antigen and little pathological changes in intestinal mucosa were found in L. acidophilus pretreated group and treated group when compared with HRV infected group. Conclusion L. acidophilus may be used as an alternative approach for the prevention and treatment of neonatal mice infected with HRV.

Objective To investigate the risk factors associated with hemorrhagic transformation after administration of thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) in patients diagnosed with acute ischemic stroke.Methods The design for this research was a case-control study-21 patients with hemorrhagic transformation after administration of thrombolytic therapy using rt-PA were categorized as cases,and 63 patients without hemorrhagic transformation after administration of thrombolytic therapy using rt-PA were categorized as controls.Univariate and multivariate logistic regression analysis were performed to analyze the risk factors associated with hemorrhagic transformation after administration of thrombolytic therapy using rt-PA in patients diagnosed with acute ischemic stroke.Results Results of univariate analysis showed that positive baseline National Institutes of Health Stroke Scale (NIHSS) scores ＞ 10,hypertension,baseline systolic blood pressure (SBP) ≥ 140 mmHg,increased blood glucose level,history of atrial fibrillation,and cerebrovascular disease (CVD) were significantly higher in the case group than in the control group.Results of multivariate logistic regression analysis showed that baseline SBP ≥ 140 mmHg (OR =14.59,95％ CI:1.63-130.95),increased blood glucose level (OR =9.92,95％ CI:0.97-101.24),and history of CVD (OR =10.75,95％ CI:1.76-65.78) were independent risk factors associated with hemorrhagic transformation after administration of thrombolytic therapy using rt-PA in patients diagnosed with acute ischemic stroke.Conclusion Baseline SBP ≥ 140 mmHg,increased blood glucose level,and history of CVD were observed to be independent risk factors associated with hemorrhagic transformation after administration of thrombolytic therapy using rt-PA in patients diagnosed with acute ischemic stroke.

Objective:To investigate the pathogenic gene locus and prenatal genetic diagnosis of 54 families with oculocutaneous albinism (OCA).Methods:This retrospective study enrolled 54 OCA probands and their families from Gansu Province Maternal and Child Health Care Hospital from May 2014 to May 2020. TYR gene variation screening was performed on the probands by Sanger sequencing. Those with negative results were analyzed by high-throughput sequencing, and further verification was performed on their parents by Sanger sequencing. Among the 54 families, 15 ml amniotic fluid were collected from 16 women at 18-21 gestational weeks in their subsequent pregnancy. Sanger sequencing combined with short tandem repeats sequence for linkage analysis were performed for genetic analysis. All data were analyzed using descriptive statistical analysis. Results:Out of the 54 OCA probands, 48 were diagnosed as OCA1, five were OCA2 and one was OCA4 based on the Sanger sequencing and high-throughput sequencing detection. A total of 26 different variation sites were involved in the 48 OCA1 probands, including 15 missense mutations, five nonsense mutations, three splicing mutations, and three frame-shift mutations, among which, c.929insC (29%, 28/96) was the most frequent mutation, followed by c.896G>A (11%, 11/96), c.832C>T (8%, 8/96) and c.703T>C (5%, 5/96). The diagnosis was confirmed in all 16 fetuses in the 16 families that underwent prenatal diagnosis. Five of them were affected and their mothers chose to terminate the pregnancies, the other 11 pregnancies continued to delivery, including seven heterozygous carriers and four fetuses without the same pathogenic allele as the proband. Maternal contamination was excluded in all prenatal samples using short tandem repeat for linkage analysis. All 11 children were in good health during telephone follow-up one month after birth. Postnatal validations were consistent with the prenatal tests.Conclusions:Genetic diagnosis could accurately identify various types of OCA and help to provide prenatal diagnosis and fertility consultation for subsequent pregnancies.

OBJECTIVE: To analyze the clinical data and genetic characteristics of a child with fibrocartilage hyperplasia type 1 (FBCG1). METHODS: A child who was admitted to Gansu Provincial Maternity and Child Health Care Hospital on January 21, 2021 due to severe pneumonia and suspected congenital genetic metabolic disorder was selected as the study subject. Clinical data of the child was collected, and genomic DNA was extracted from peripheral blood samples from the child and her parents. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. RESULTS: The patient, a 1-month-old girl, had presented with facial dysmorphism, abnormal skeletal development, and clubbing of upper and lower limbs. WES revealed that she has harbored compound heterozygous variants c.3358G>A/c.2295+1G>A of the COL11A1 gene, which has been associated with fibrochondrogenesis. Sanger sequencing has verified that the variants have been respectively inherited from her father and mother, both of whom were phenotypically normal. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.3358G>A variant was graded as likely pathogenic (PM1+PM2_Supporting+PM3+PP3), and so was the c.2295+1G>A variant (PVS1＋PM2_Supporting). CONCLUSION The compound heterozygous variants c.3358G>A/c.2295+1G>A probably underlay the disease in this child. Above finding has facilitated definite diagnosis, genetic counseling for her family.
Female ; Humans ; Infant ; Abnormalities, Multiple ; Collagen Type XI/genetics* ; Genetic Counseling ; Genomics ; Mutation

OBJECTIVE: To explore the genetic basis for a child with concomitant spinal muscular atrophy (SMA) and Citrin protein deficiency. METHODS: The child was subjected to whole exome sequencing by using target sequence capture high-throughput sequencing. Candidate variants were verified by Sanger sequencing. The SMN genes of the patient were also analyzed through multiplex ligation-dependent probe amplification (MLPA). RESULTS: The patient was found to carry homozygous deletion of exons 7 and 8 of the SMN1 gene, for which his parents were both carriers. The patient also carried compound heterozygous variants c.1737G>A and IVS16ins3kbof the SLA25A13 gene, in addition with compound heterozygous variants c.948G>A and c.2693T>C of the POLG gene, for which his parents were carriers, too. CONCLUSION Variants of the SLC25A13 gene probably underlay the deficiency of Citrin protein, which may lead to neonatal intrahepatic cholestasis (NICCD). The patient also had SMA. The compound heterozygous variants c.948G>A and c.2693T>C of the POLG gene are likely to cause mitochondrial DNA deletion syndrome type 4A, though other types of mitochondrial disease cannot be excluded.

OBJECTIVE: To analyze the clinical phenotype and results of genetic testing in three children with Cornelia de Lange syndrome (CdLS). METHODS: Clinical data of the children and their parents were collected. Peripheral blood samples of the pedigrees were collected for next generation sequencing analysis. RESULTS: The main clinical manifestations of the three children have included growth delay, mental retardation, peculiar facies and other accompanying symptoms. Based on the criteria proposed by the International Diagnostic Consensus, all three children were suspected for CdLS. As revealed by whole exome sequencing, child 1 has harbored NIPBL gene c.5567_5569delGAA insTAT missense variant, child 2 has harbored SMC1A gene c.607A>G missense variant, and child 3 has harbored HDAC8 gene c.628+1G>A splicing variant. All of the variants were de novo in origin. CONCLUSION All of the children were diagnosed with CdLS due to pathogenic variants of the associated genes, among which the variants of NIPBL and HDAC8 genes were unreported previously. Above finding has enriched the spectrum of pathogenic variants underlying CdLS.
Humans ; Cell Cycle Proteins/genetics* ; De Lange Syndrome/diagnosis* ; Genotype ; Phenotype ; Genetic Testing ; Histone Deacetylases/genetics* ; Repressor Proteins/genetics*

OBJECTIVE: To carry out pedigree analysis for a rare child with comorbid X-linked ichthyosis (XLI) and Duchenne muscular dystrophy (DMD). METHODS: Whole exome sequencing (WES) and multiple ligation-dependent probe amplification (MLPA) were used to detect potential deletions in the STS and DMD genes. RESULTS: The proband was found to harbor hemizygous deletion of the STS gene and exons 48 to 54 of the DMD gene. CONCLUSION The child has comorbid XLI and DMD, which is extremely rare.
Child ; Dystrophin/genetics* ; Exons ; Gene Deletion ; Genetic Testing ; Humans ; Ichthyosis/genetics* ; Muscular Dystrophy, Duchenne/genetics* ; Mutation

OBJECTIVE: To explore the clinical features and genetic basis for a child with 3-methylglutaconic aciduria type VII. METHODS: A child who was diagnosed at the Gansu Provincial Maternity and Child Health Care Hospital on August 9, 2019 was selected as the study subject. Clinical data of the child, including urine gas chromatography and mass spectrometry, were collected. The child and her parents were subjected to whole exome sequencing. RESULTS: The child, a female neonate, had presented mainly with intermittent skin cyanosis, convulsions, hypomagnesemia, apnea, neutropenia after birth. Her urine 3-methylpentenedioic acid has increased to 17.53 μmol/L. DNA sequencing revealed that she has harbored compound heterozygous variants of the CLPB gene, namely c.1016delT (p.L339Rfs*5) and c.1087A>G (p.R363G), which were respectively inherited from her mother and father. Both variants were unreported previously. Based on the standards from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively predicted to be pathogenic and likely pathogenic. CONCLUSION The child was diagnosed with 3-methylglutenedioic aciduria type VII. Discovery of the c.1016delT and c.1087A>G variants has enriched the mutational spectrum of the CLPB gene.
Female ; Humans ; Infant, Newborn ; Pregnancy ; Base Sequence ; Metabolism, Inborn Errors/diagnosis* ; Mutation ; Neutropenia/genetics* ; Sequence Analysis, DNA

Objective To explore the clinical features, cytogenetic and molecular genetics characteristics of trisomy 12 p in neonates. Method The clinical data were reviewed in a neonate with trisomy 12 p confirmed by routine G-banding chromosome karyotype analysis, high throughput sequencing chromosome copy number variation analysis (CNV) and lymphocyte interphase fluorescence in situ hybridization (FISH) . Results The chromosome karyotype in peripheral blood of the neonate was 47, XX, +mar, and the karyotypes of her parents were normal. CNV detected a regional duplication of 12 p13.33-p11.1 (160001-34860000) with a fragment size of 34.7 Mb. Peripheral blood lymphocyte interphase FISH showed that there were 3 signals in the short arm of chromosome 12 in all interphase nuclei of the neonate, and no chimera existed. It was finally confirmed to be trisomy 12 p. Conclusion The combination of clinical features, peripheral blood karyotype analysis, CNV and FISH techniques can effectively confirm the diaganosis of trisomy 12 p.