RESUMO
OBJECTIVE@#To explore the genetic basis for a child with unexplained global developmental delay (GDD), seizure, and facial deformity.@*METHODS@#Whole exome sequencing (WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of the patient and his parents.@*RESULTS@#WES revealed that the patient has carried a previously unreported de novo heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene, Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.4906C>T variant of KMT2A gene was predicted to be pathogenic (PVS1+ PS2+ PM2+PP3).@*CONCLUSION@#The heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene probably underlay the disease in the child. Above finding has enriched the spectrum of pathogenic variants of the KMT2A gene.
Assuntos
Criança , Humanos , Masculino , Anormalidades Múltiplas/genética , Histona-Lisina N-Metiltransferase/genética , Deficiência Intelectual/genética , Proteína de Leucina Linfoide-Mieloide/genética , SíndromeRESUMO
Objective To investigate the change in distribution and antimicrobial resistance of pathogens from blood culture of children,and provide a basis for treatment of bloodstream infection.Methods Pathogens isolated from blood culture of hospitalized children between January 2009 and December 2013 were divided into group 2009-2011 and 2012-2013.Distribution and antimicrobial susceptibility of pathogens were analyzed.Results From 2009 to 2013,a total of 48 455 blood specimens were taken for culture,2 730 pathogenic bacteria were isolated,positive rate was 5.63%.The positive rate of blood culture decreased year-by-year (χ2 =415.30,P <0.01 ).Of 2 730 iso-lates of pathogenic bacteria,gram-positive bacteria,gram-negative bacteria,and fungi accounted for 80.37% (n =2 194),18.68%(n=510),and 0.95%(n=26)respectively.The difference between two groups of pathogenic bacte-ria was significant(χ2 =180.334,P <0.001).Susceptibility rates of gram-positive cocci to vancomycin,linezolid and teicoplanin were all 100%,resistance rates of coagulase-negative Staphylococcus and Staphylococcus aureus to cip-rofloxacin,compound sulfamethoxazole and tetracycline all decreased.Susceptibility rates of gram-negative bacilli to imipenem,meropenem and amikacin were all≥97.50%,susceptibility rate of Klebsiella pneumoniae to levofloxacin was 100%;Of cephalosporins,Escherichia coli and Klebsiella pneumoniae had high resistance except ceftazidime and cefepime.Conclusion Distribution of pathogens from blood culture of children in 2009-2013 changed signifi-cantly,pathogens have high resistance to commonly used antimicrobial agents,more attention should be paid to the monitor of pathogens from blood culture and pathogenic antimicrobial resistance.
RESUMO
Objective To investigate the relationship between genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) and the risk of childhood acute lymphocytic leukemia (ALL).Methods 45 patients with ALL and a cohort of 45 matched healthy children were included,and DNA was extracted from their peripheral blood.PCR-RFLP was used to determine the genotypes of MTHFR C677T and A1298C.The adjusted odds tatio (OR) and 95 ％ confidence interwal (CI) were calculated using unconditional logistic regression model.Results The frequency of MTHFR 677 CC,CT and TT genetypes were 31.1％ (14/45),51.1％ (23/45) and 17.7 ％ (8/45) in controls and 51.1％ (23/45),40.0 ％ (18/45) and 8.9 ％ (4/45)in ALL,respectively (x2 =7.48,P =0.04).The frequency of MTHFR 677 T allele were 69.9 ％ (31/45) in controls and 48.8 ％ (22/45) in ALL.The MTHFR 677 T allele had an decreased risk in ALL compared with CC genetype (OR =0.4,95 ％ CI 0.21-0.83).The frequency of MTHFR 1298 AA,AC and CC genetypes were 57.8 ％,40.0 ％ and 2.2 ％ in controls and 18.8 ％,44.4 ％ and 6.8 ％ in ALL,respectively (x2 =11.23,P=0.23).The frequency of MTHFR 1298 C allele were 51.1％ (23/45) in controls and 42.2 ％ (19/45) in ALL.No significant association between the MTHFR 1298 polymorphism and the risk of ALL (OR =1.3,95 ％ CI 0.21-0.83).Conclusion MTHFR 677 polymorphism could significantly decrease the risk of developing childhood ALL,whereas MTHFR 1298 don' t significantly affect the risk of ALL.
RESUMO
Objective To study the over-expression and clinical implications of the oncogene MDM2 in acute leukemia (AL). Methods The expression of MDM2 gene in 100 patients with newly diagnosed and relapse or refractory AL and 20 healthy as control was measured by relative quantitative reverse transcriptase polymerase chain reaction (RT-PCR),then the results was measured by χ2-test,t-test and one-way ANOVA to compare expession positive rate and intensity of MDM2. Results Among 100 patients,fifty-eight had the high expression of MDM2 gene (58 %). The expression level of MDM2 gene in patients was higher than that of health controls(P ＜0.05). The expression positive rate of MDM2 is higher in poor outcome group (67.9 %,19/28)than that in general outcome group (33.9%,19/56) (P＜0.05). Conclusion Our results suggest that the expression of MDM2 gene plays an important role in the pathogenesis and poor outcome of AL.
RESUMO
Objective To analyse the fusion genes derived from chromosome structural aberrations in acute myeloid leukemia(AML) and the relationship between fusion genes and the MICM classification, clinical diagnosis, chemotherapy and prognosis. Methods The expression of fusion gene in bone marrow samples was detected with multiplex RT-PCR technique and chromosome karyotypes, immunological phenotypes and clinical data were analyzed in 60 acute myeloid leukemia newly diagnosed. Results 37 cases(61.67 %) of 60 patients carried 5 kinds of fusion genes consisting of MLL-AF9, TLS-ERG, CBFβ-MYH1, AML1-ETO and PML-RARα. The activation of oncogene HOX11 was detected in 13 AML cases, three of them with other chromosome aberration simultaneously.23 cases of 31 patients carrying AML1-ETO or PML-RARα, reached complete remission(CR) after chemotherapy and without relapse. Conclusion Gene typing is the most precise classification method that can direct clinical treatment and evaluate prognosis. Multiplex RT-PCR technique, which can quickly screen 29 kinds of fusion gene derived from chromosome structural aberrations at one time, maybe helpful to improve M1CM classification and guide the choice of treatment.
RESUMO
Objective To detect expression of TEL-AML1 fusion genes in pediatric cases with acute lymphoblastic leukemia(ALL) and discuss the role of reverse transcriptase polymerase chain reaction(RT-PCR)and fluorescence in situ hybridization(FISH) in detection of t(12 ;21) and the clinical significance. Methods TEL-AML1 fusion gene was identified in bone marrow munonuclear cells from 31 newly diagnosed childhood ALL patients by NRT-PCR, FISH and conventional cytogenetic analysis (CCA). Results TEL-AML1 fusion gene was found in 7 out of 31 cases, accounting for 22.6 % in pediatric ALL, and 7 out of 31 cases accounting for 25.9 % in B-ALL Seven cases were found with t (12;21) by FISH and NRT-PCR. The incidence of the t(12;21) was 22.6 % in newly diagnosed pediatric ALLs. Conclusion It is concluded that TEL-AML1 rearrangement is a frequent molecular abnormality in childhood ALL. t(12;21) is the most common cytogenetic translocations in Chinese pediatric ALLs, but it is always difficult to identify by routine CCA.Other molecular methods, e.g. NRT-PCR and FISH are powerful in detecting such a critical genetic translocation.
RESUMO
Objective To investigate the value of interphase fluorescence in situ hybridization(FISH)technique and the detection of fusion gene in the diagnosis of acute myeloid leukemia(AML)M2 and M3 Methods FISH was used to detect the AML1/ETO fusion gene and/or PML/RARα fusion gene in incipient cases including 9 AML-M2, 12 AML-M3 and 10 AML undetermined as AML-M2 or AML-M3 primarily diagnosed by routine morphology though bone marrow,cytochemical staining and immunophenotyping,which can help diagnose and guide clinical therapy.Results 4 of 9 AML-M2 cases were AML1/ETO positive.Among 12 AML-M3 cases,10 were PML/RARα positive.1 case was detected AML1/ETO fusion gene.In 10 untonfirmed M3 or M2,3 case8 showed AML1/ETO,5 showed PMIJRARot fusion gene and the rest showed neither of the genes.Conclusion As a new technique of the molecular genetics,FISH is accurate, rapid and efficient.It would be of significance not only at diagnosis of AML,but also for subsequent clinical decision-making.