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Objective:To investigate the performance of chromosome karyotype, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) in prenatal diagnosis of true fetal chromosome mosaicism. Methods:This retrospective study enrolled 40 women with true fetal chromosome mosaicism from 4 071 singleton pregnant women who were indicated for and underwent amniocentesis or/and cordocentesis in the the First Affiliated Hospital of Sun Yat-sen University from April 2018 to August 2021. The results of chromosome karyotyping, CMA and FISH, the types of chromosomal mosaicism, mosaicism ratio and pregnancy outcomes were analyzed using Chi-square test. Results:(1) The detection rate of true fetal mosaicism was 0.98% (40/4 071). (2) Sex chromosome mosaicism accounted for 42.5% (17/40). Other chromosomal mosaicism involved chromosomes 21, 22, 18, 16, 7, 12, 15, 17 and 20, as well as balanced chromosomal translocation. (3) The detection rate of true fetal mosaicism by chromosome karyotyping was 77.4% (24/31) from amniotic fluid samples and 10/19 from umbilical cord blood samples, while that data by CMA was 76.7% (23/30) and 7/11,respectively. (4) Of the 40 pregnant women with fetal chromosome mosaicism, FISH test was performed on 20 cases (14 cases were verified with both amniotic fluid and umbilical cord blood samples, five with amniotic fluid samples and one with umbilical cord blood sample), and all of the diagnosis of mosaicism were confirmed. For those with mosaicism ratio <30%, the detection rate by FISH was higher than that by CMA among amniotic fluid samples [14/19 vs 43.5% (10/23), χ2=3.88, P=0.049]. (5) Among the 40 pregnant women, five were lost to follow-up; 18 chose to terminate the pregnancy; and 17 continued the pregnancy to delivery. No abnormalities in mental or physical development were reported in the 17 neonates after birth or during on-line follow-up between 6 to 24 months old. Of the 14 pregnant women with mosaicism ratio <30% which confirmed by FISH, eight chose to continue the pregnancy, and no abnormalities in mental development or growth were found in the neonates. Conclusions:In prenatal diagnosis of true fetal choromosome mosaicism, the incidence of sex chromosome mosaicism is the highest. FISH may improve the prenatal diagnosis rate of mosaicism and is more accurate in determining the mosaicism ratio. The combination of FISH, CMA and chromosome karyotyping would significantly improve the detection rate of chromosomal mosaicism and assess the mosaicism ratio more accurately, which is of great value in clinical consultation and evaluation of fetal prognosis.
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Objective@#To investigate the application values of immunophenotypic analysis and molecular genetics in the diagnosis of acute promyelocytic leukemia (APL) .@*Methods@#The retrospective analyses of flow cytometric (FCM) immunophenotypic anyalysis, chromosome karyotype and chromosome fluorescence in situ hybridization (FISH) of 798 outpatient or hospitalization APL patients referred to our hospital between May 2012 and December 2017 were performed to further study the application values of FCM and molecular genetics in the diagnosis of APL.@*Results@#The sensitivity and specificity of FCM were 91.9% and 98.7% respectively. The typical characteristic immunophenotype for APL was as of follows: a high SSC, absence of expression of cluster differntiation (CD) CD34 and HLA-DR, and expression or stronger expression of CD33, consistent expression of CD13, CD9, CD123, expression of CD56, CD7, CD2 (sometimes) . The rest 10% of the cases harbored atypical APL phenotypes, generally accompanied by CD34 and/or HLA-DR expression, decreased SSC and often accompanied by CD2 expression, it was difficult to definitively diagnose APL by this FCM phenotype, and their diagnoses depended on the results of genetics or molecular biology tests. Compared with normal individuals, complex karyotypes APL with t (15;17) translocation, other variant translocations and variant t (11;17) , t (5;17) had no significant differences in terms of their FCM phenotypes.@*Conclusions@#FCM could rapidly and effectively diagnose APL. Despite the fact that complex karyotypes with various additional chromosomal abnormalities were detected in approximately one third of APL cases in addition to the pathognomonic t (15;17) (q22;q21) , they had no observable impact on the overall immunophenotype. Molecular and genetic criteria were the golden criteria for the diagnosis of APL. About 10% of immunophenotyping cases relied on molecular genetics for diagnosis.
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Objective@#To investigate the correlation between fetal cranial nervous system malformation and chromosome abnormality.@*Methods@#The pregnant women with fetal cerebral nervous system dysplasia were collected from January 2013 to August 2018 at the Prenatal Diagnostic Center of the Sixth Affiliated Hospital of Guangzhou Medical University.The fetus was diagnosed by ultrasonography and karyotype analysis.@*Results@#A total of 18 cases of abnormal karyotypes were detected from 85 patient samples, and the abnormal rates were 21.18%.Single cranial nervous system malformation was found in 47 cases, abnormal karyotypes in 4 cases, multiple system malformation in 38 cases, and abnormal karyotypes in 14 cases, and the abnormal karyotype rate of multiple system malformation was higher than that of single cranial nervous malformation (36.84% vs.8.51%, χ2=10.101, P=0.001 5). And the 88.89%(16/18 cases)of abnormal karyotypes were founded in the early and middle pregnancy (≤28 weeks). The abnormal karyotype detection rates of cranial nervous system malformation associated with cardiovascular, skeletal and limb, facial neck abnormalities were 58.82% (10/17 cases), 50.00% (6/12 cases) and 50.00% (9/18 cases), respectively.In the fetal phenotypes, the abnormal karyotype detection rates of choroid plexus cysts were up to 64.29%, followed by arachnoid cysts (50.00%), craniocerebral abnormalities (45.45%) and holoprosencephaly (36.36%).@*Conclusions@#Chromosomal aneuploidy or structural abnormalities can lead to abnormal development of the fetal cranial nervous system, in which the rates of abnormal karyotypes on fetal cranial nervous with cardiovascular malformation and choroid plexus cysts are the highest.
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Objective@#To report on a case of maternally derived 45, X mosaicism detected by non-invasive prenatal testing (NIPT).@*Methods@#Fetal sex chromosomal abnormality was detected by NIPT. Maternally derived 45, X mosaicism was confirmed by chromosome karyotype analysis. Fetal sex chromosome aneuploidy was detected by amniotic fluid chromosome microarray analysis.@*Results@#A maternal 45, X mosaicism was diagnosed. The fetus was confirmed to be normal.@*Conclusion@#Maternal 45, X masaicism can be diagnosed by NIPT.
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Objective: To investigate the application values of immunophenotypic analysis and molecular genetics in the diagnosis of acute promyelocytic leukemia (APL) . Methods: The retrospective analyses of flow cytometric (FCM) immunophenotypic anyalysis, chromosome karyotype and chromosome fluorescence in situ hybridization (FISH) of 798 outpatient or hospitalization APL patients referred to our hospital between May 2012 and December 2017 were performed to further study the application values of FCM and molecular genetics in the diagnosis of APL. Results: The sensitivity and specificity of FCM were 91.9% and 98.7% respectively. The typical characteristic immunophenotype for APL was as of follows: a high SSC, absence of expression of cluster differntiation (CD) CD34 and HLA-DR, and expression or stronger expression of CD33, consistent expression of CD13, CD9, CD123, expression of CD56, CD7, CD2 (sometimes) . The rest 10% of the cases harbored atypical APL phenotypes, generally accompanied by CD34 and/or HLA-DR expression, decreased SSC and often accompanied by CD2 expression, it was difficult to definitively diagnose APL by this FCM phenotype, and their diagnoses depended on the results of genetics or molecular biology tests. Compared with normal individuals, complex karyotypes APL with t (15;17) translocation, other variant translocations and variant t (11;17) , t (5;17) had no significant differences in terms of their FCM phenotypes. Conclusions: FCM could rapidly and effectively diagnose APL. Despite the fact that complex karyotypes with various additional chromosomal abnormalities were detected in approximately one third of APL cases in addition to the pathognomonic t (15;17) (q22;q21) , they had no observable impact on the overall immunophenotype. Molecular and genetic criteria were the golden criteria for the diagnosis of APL. About 10% of immunophenotyping cases relied on molecular genetics for diagnosis.
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Humans , Flow Cytometry , Immunophenotyping , In Situ Hybridization, Fluorescence , Leukemia, Promyelocytic, Acute/diagnosis , Retrospective StudiesABSTRACT
Objective To investigate the correlation between fetal cranial nervous system malformation and chromosome abnormality.Methods The pregnant women with fetal cerebral nervous system dysplasia were collected from January 2013 to August 2018 at the Prenatal Diagnostic Center of the Sixth Affiliated Hospital of Guangzhou Medical University.The fetus was diagnosed by ultrasonography and karyotype analysis.Results A total of 18 cases of abnormal karyotypes were detected from 85 patient samples,and the abnormal rates were 21.18％.Single cranial nervous system malformation was found in 47 cases,abnormal karyotypes in 4 cases,multiple system malformation in 38 cases,and abnormal karyotypes in 14 cases,and the abnormal karyotype rate of multiple system malformation was higher than that of single cranial nervous malformation (36.84％ vs.8.51％,x2 =10.101,P =0.001 5).And the 88.89％ (16/18 cases) of abnormal karyotypes were founded in the early and middle pregnancy (≤ 28 weeks).The abnormal karyotype detection rates of cranial nervous system malformation associated with cardiovascular,skeletal and limb,facial neck abnormalities were 58.82％ (10/17 cases),50.00％ (6/12 cases) and 50.00％ (9/18 cases),respectively.In the fetal phenotypes,the abnormal karyotype detection rates of choroid plexus cysts were up to 64.29％,followed by arachnoid cysts (50.00％),craniocerebral abnormalities (45.45％) and holoprosencephaly (36.36％).Conclusions Chromosomal aneuploidy or structural abnormalities can lead to abnormal development of the fetal cranial nervous system,in which the rates of abnormal karyotypes on fetal cranial nervous with cardiovascular malformation and choroid plexus cysts are the highest.
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[Objective] To analyze blood lipid and its related factors in Chinese children and adolescents with Turner syndrome.[Methods] The untreated TS patients were divided into two groups according to age (＜11 years old and 11～15 years old) and enrolled two groups of age-matched control girls,blood lipid and the incidence of dyslipidemia were compared between the four groups,the related factors of blood lipid were also analyzed.Moreover,TS patients were divided into two groups according to karyotype,including 45,XO karyotype (55 cases) and other karyotypes (53 cases),blood lipid and the incidence of dyslipidemia in two groups were compared.[Result] Compared to age-matched control girls,TS patients of age 11～15 years group had higher TG levels and higher incidence of hypertriglyceridemia and borderline-hypertriglyceridemia (P＜0.05) and the incidence of borderline-hypercholesterolemia was also significantly higher (P＜0.01).But there were no differences in blood lipid level,incidence of dyslipidemia and the incidence of borerline-dyslipidemia between TS patients who were less than 11 years old and age-matched control girls.Total cholesterol of TS patients was negatively related to bone age (P＜0.05).Triglyceride of TS patients was positively related to waist circumference (P＜0.01).TS patients of 45,XO karyotype had lower TG levels,higher HDL levels and lower incidence of low HDL,borderline-high non-HDL and borderline-hypertriglyceridemia compared with those of other karyotypes (P＜0.05).[Conclusions] Triglyceride in TS patients of age 11-15 years were higher than the control subjects,which may be related to estrogen deficiency and chromosome karyotype.
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Objective To analyze the genetic characteristics of chromosomes and related fusion genes in acute myeloid leukemia (AML) (non-M3), and to evaluate the prognosis of patients with chemotherapy of DA regimen with different doses of daunorubicin. Methods Fifty-six patients with newly diagnosed non-M3 AML from January 2013 to January 2015 were collected. Adopted short-term culture method was used to treat bone marrow, R-binding chromosome karyotyping was used to detect cytogenetic. Thirty-one types of fusion gene were identified by PCR and 10 % agarose gel electrophoresis. All patients treated by DA regimen were divided into group A, group B and group C according to different dosage of daunorubicin. Then, complete remission (CR) rate and survival time in the 3 groups were observed. The effect of cytogenetic and molecular biology abnormality on the chemotherapy, CR rate and overall survival (OS) of the 3 groups were analyzed by the chi-square test. Results Among the 56 patients, 18 cases (32.1%) had abnormal chromosome karyotype, 6 cases (10.7 %) had abnormal number of chromosome, 16 cases (28.6 %) had abnormal structure of chromosome, and 4 cases (7.1 %) had both abnormal number and structure of chromosome. Meanwhile, the most common abnormal structure was t(8;21), and the most common abnormal quantity were+8, -Y. Detective rate of genetic abnormality was raised to 62.00 % through fusion gene and chromosome karyotype analysis. The total CR rate of DA-induced chemotherapeutic regimen was 73.2 %, and the two-year OS rate was 42.9%. The remission rate of chemotherapy in the middle-risk group was significantly lower than that in the low-risk group (χ 2 = 8.976, P = 0.002), but there was no significant difference between the low-dose chemotherapy group and the standard dose chemotherapy group (P>0.05). The standard dose group showed a significant advantage in the OS rate (χ2= 8.045, P= 0.005). Conclusions Adult acute leukemia has its unique cytogenetic characteristics, which can assist in guiding clinical diagnosis, classification and prognosis. The prognosis of middle-risk patients is significantly lower than the low-risk group. Low-risk patients could benefit from a reduced dose of DA regimen, but the standard dose DA regimen has a significant advantage in long-term survival.
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Objective To make the chromosome karyotype analysis of 130 patients with leukemia by using the improved chromosome short-term culture method.Methods We optimized the main factors with a single factor gradient experiment in short-term culture of bone marrow chromosome, including colchicines concentration, duration of action of colchicines,and hypotonic time.On this basis,we conducted the three-factors and three-level orthogonal experiment to achieve improved bone marrow chromosome preparation system,which was later applied in 130 patients with leukemia in our hospital.Results The orthogonal experiment results showed that the optimum conditions were colchicines concentration of 0.07 μg/mL,colchicines action time of 80 min,and hypotonic time of 35 min during the preparation of the bone marrow chromosome.Using this method,the chromosome preparation success rate reached 97.69% and the detection rate of abnormal karyotype reached 82.3% in the chromosome karyotype analysis.Conclusion Bone marrow chromosome preparation system with colchicines concentration of 0.07 μg/mL and colchicines action time of 80 min,and hypotonic time of 35 min is worthy of clinical promotion.
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Objective To evaluate the value of nuchal translucency (NT) thickness in the fetal chromosome abnormality screening. Methods 11 086 pregnant women received NT measurement in 11 ~ 13+6 weeks at Hainan general hospital from January 2010 to December 2014 were selected in the study. The NT thickness was measured according to guidelines from Fetal Medicine Foundation. 122 fetuses (NT≥2.5 mm) were recruited to accept karyotype analysis. Results 11 086 pregnant women received NT measurement in 11 ~13+6 weeks, in which 122 cases′ NT are more than or equal to 2.5 mm, with a positive rate of 1.10%. 122 cases of fetal NT thickening are between 2.5 to 12.0 mm, with the average degree at (4.5 ± 2.1)mm. 122 invasive prenatal diagnostic specimens chromosome karyotype analysis results showed chromosomal abnormalities in 21 cases (abnormal rate of 17.2%), the abnormal chromosome number in 17 cases and abnormal structure in 4 cases. The top 3 are trisomy 21 (12 cases, 57.1%), chromosome pericentric inversion (3 cases, 14.3%), and trisomy 18 (2 cases, 9.5%). Fetal chromosomal abnormalities resulting from different childbirth age, the sex of the fetus, NT thickness showed significant statistical difference (P < 0.05). The concrete manifestation is that fetal chromosomal anomaly detection rate in childbirth by women more than 35 years old age are higher than other age. Female fetal chromosomal anomaly detection rate is higher than the male , and NT thickness of 5mm of fetal chromosomal abnormality rate is significantly higher than the thickness of NT group at 2.5mm~ and 3.5mm~. Fetal NT thickening of NT measurements was in significant positive correlation with fetal chromosome abnormal rate (χ2=15.533, P < 0.001). Logistic regression analysis found that with a higher NT thickness , risk of fetal chromosomal abnormalities would be significantly higher , and thickening of NT could be an independent predictor of fetal chromosome abnormalities. Conclusion In early pregnancy, ultrasound examination of fetal ultrasound screening of NT thickness can be used as an important index of fetal chromosomal abnormality , and interventional diagnosis of prenatal NT thickness increase could pose increased risk of fetal chromosomal abnormalities.
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Objective To explore the abnormal karyotype characteristics of myelodysplastic syndrome (MDS)patients and their correlation with clinical prognosis.Methods Analyzed the karyotypes of 281 MDS patients by use of G-banding tech-nique.Results Through analysis of the karyotypes of 281 MDS patients,found that the percentage of abnormal karyotypes was 48.75% (137/281),among 137 patients with abnormal karyotypes,43.07% (59 cases)presented with numerical aber-ration,31.39% (43 cases)with structural aberration,and 25.54% (35 cases)with both numerical and structural abnormali-ties.As for MDS subtypes,the occurrence rate of abnormal karyotype was 63.41% (26/41)in RAEB-2,58.73% (37/63)in RAEB-1,39.2% (49/125)in RCMD,15.38% (2/13)in RAS and 22.58% (7/31)in RA.The rates of abnormal karyotype in RAEB-1 and RAEB-2 were significantly higher than that in RA and RAS(P<0.01),and in RCMD (P <0.05).The fre-quent abnormal karyotypes were as follows:+8,-7/7q-,-20/20q-,complex karyotypes chromosomal translocation,i(17),-Y and +21.The follow-up study of 159 MDS patients indicated that the median survival time was 39 months for 68 patients with normal karyotypes and 21 months for 91 patients with abnormal karyotypes,the former was significantly prolonged than the latter (P < 0.05).As far as the leukemia transition rate was concerned,the patients with aberrant karyotypes (35.5%)were significantly higher than that with normal karyotypes (10.3%)(P < 0.01),among them,the cases with complex karyotypes and-7/7q-more easily transit into leukemia.Conclusion MDS was one kind of clonal hematological ma-lignancy with high heterogeneity.Chromosomal karyotype test plays an important role in the correct diagnosis,typing and prognosis evaluation of MDS.
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Objective To study the immunophenotype and chromosome karyotype of 57 adult patients with newly?diagnostic acute lymphoblastic leukemia(ALL). Methods The immunophenotype and chromosome karyotype of 57 adult patients with newly?diagnostic ALL were determined by using flow cytometer and karyotyping,and then the clinical characteristics and significance were analyzed. Results In patients with B cell acute lymphoblastic leukemia(B?ALL),the expression of CD19 and CD22 were significantly higher than CD10 and CD20(P<0.05). The expression of CD7 and CD3 were much higher in patients with T cell acute lymphoblastic leukemia(T?ALL). As for the early antigen,patients of all subtypes of ALL showed high expression rate of CD34 and CD38. In addition,the HLA?DR was only detected in B?ALL. There was no difference in comparison with clinical characteristics,total rate of CR and rate of relapse between ALL with and without myeloid antigen expression. The expression rate of CD34 and HLA?DR was higher in My+?ALL(P<0.05). The relapse rate was much higher in these patients with abnormal karyotype than other pa?tients(P<0.05). Patients with high?risk karyotype showed higher expression rates of CD20 and CD3 than those with standard?risk. Conclusion The immunophenotypes and chromosome karyotypes show obviously heterogeneous features,and the patients with abnormal karyotypes have higher relapse rate. These above mentioned methods are applicable for the diagnosis and individualized treatment of ALL patients.
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Objective To explore the clinic value of chromosome karyotype analysis of amniotic fluid cells in prenatal diagnosis . Methods 1 466 cases of pregnant women who had the prenatal diagnosis indexes were selected ,and their amniotic fluid specimens were collected through amniocentesis guiding by type‐B ultrasonic around the 16th to 24th week .Amniotic fluid cells were gained after a successful cell culture .G banding was used for the karyotype analysis of amniotic fluid cells .Results The one‐time success rate of cultivation for amniotic fluid cells was 99 .8% .In 1 466 cases of pregnant women ,there were 16 cases of abnormal karyotype polymorphism (including 12 cases of trisomy 21 ,1 case of trisomy 18 ,and 3 cases of Chromosome abnormalities) and 3 cases of chromosomal polymorphism .Conclusion The chromosome karyotype analysis of amniotic fluid cell is still an irreplaceable test in prenatal diagnosis .
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Objective To explore the significance of dysplasia and cytogenetic changes to the diagnosis and typing of myelodysplastic syndrome (MDS).Methods The dysplasia performance of each series in every isoforms was observed by the bone marrow aspiration and peripheral blood smear to the 132 patients with MDS. At the same time do the chromosome karyotype was analizad combined with morbidness cells and chromosome karyotype abnormal analysis associated with MDS subtype. Resuits Acorrding to the dysplasia ≥0.10, the totle detection rate of granulocyte series, erythrocyte series and megakaryocytic was 43.4 ％.The morbidness granulocyte and megalokaryocyte ≥0.10was mainly in RCMD (P ＜ 0.01); morbidness erythrocytes≥0.10 mainly in RA + RARS (P ＜ 0.01). the totle detection rate of chromosome karyotype abnormal in MDS was 44.0 ％.The detection rate in RA and RARS was lower than other isoforms,but showed no statistically significant (P ＞ 0.05).the relationships of dysplasia and chromosome karyotype abnormal with the isoforms of MDS:in RA group,50.0 ％(3/6) patients had karyotype abnormal simultaneous the detection of morbidness cells≥0.10, 76.0 ％(19/25) in RCMD group and 60.9 ％(14/23) in RAEB group (P ＜ 0.01).Conclusion Theve is relationships between the patients with chromosome karyotype abnormal and dysplasia ≥0.10 and the isoforms of MDS. Closely monitoring the hemopoiesis and cytogenetic changes is significance to diagnose MDS.
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Objective To research on and analyze the relationship between the clinical situation and karyotype of 30 patients with Turner syndrome (TS).Methods Lymphocytes of peripheral blood were cultured,then karyotyped by G banding and R banding technique.The relationship between clinical situation and karyotype of patients with TS were analyzed.Results The karyotype of TS could be divided into 4 groups:45,XO;mosaicism;with aberration of X chromosome structure and with Y chromosome.The mosaicism was the most popular.The more abnormal karyotype was,the more typical sexual non-development.Conclusion The typical patients with TS had the clinical features of microsomia,menoschesis,sexual non-development and special somatotype.The different clinical features are decided by the degree of abnormal karyotype and the proportion between abnormal cells and normal cells.Besides,the patients with TS who have Y chromosome always show hemaphrodism and must be taken ganadectomy.