Abnormal Chromosome Karyotype Research Articles

Chromosome analysis of foetal tissue from 1903 spontaneous abortion patients in 5 regions of China: a retrospective multicentre study

BackgroundAbnormal foetal tissue chromosome karyotypes are one of the important pathogenic factors for spontaneous abortion (SA). To investigate the age and abnormal foetal karyotypes of 1903 couples who experienced SA.MethodsA retrospective multicentre study collected age and foetal tissue karyotypes CNV-seq data of 1903 SA couples from 6 hospitals in 5 regions from January 2017 to March 2022. The distribution and correlation of abnormal foetal tissue karyotypes were evaluated by using regions and age.ResultsIn our study, 1140 couples (60.5% of the total) had abnormal foetal tissue chromosome karyotypes in all regions. We found that there were differences in the number of abnormal foetal tissue chromosome karyotypes, of which the incidence of trisomy was higher. At the same time, the populations situated in the eastern region had a more triploid (15.5%) distribution, trisomy (58.1%) in the southern region, mosaicism (14.8%) and microduplication (31.7%) in the southwestern region, microdeletion (16.7%) in the northern region. There are variances across areas, and it is more common in the north. The incidence risk of prenatal chromosomal abnormalities varied according to age group.ConclusionThe findings of this study suggest that the karyotypes of patients with abnormal foetal tissue chromosome abortion in different regions were different. Meanwhile, patients ≥ 35 years old had a higher risk of abnormal foetal tissue chromosome abortion.

Fetal hyperechoic kidney cohort study and a meta-analysis.

Objective: To investigate the positive rate of chromosomal and monogenic etiologies and pregnancy outcomes in fetuses with hyperechoic kidney, and to provide more information for genetic counseling and prognosis evaluation. Methods: We performed a retrospective analysis of 25 cases of hyperechoic kidney diagnosed prenatal in the Second Affiliated Hospital of Harbin Medical University and Harbin Red Cross Central Hospital (January 2017-December 2022). Furthermore, we conducted a meta-analysis of a series of hyperechoic kidneys (HEK) in the literature to assess the incidence of chromosomal and monogenic etiologies, mortality, and pooled odds ratio (OR) estimates of the association between the incidence of these outcomes and other associated ultrasound abnormalities. Results: 25 fetuses of HEK were enrolled in the cohort study, including 14 with isolated hyperechoic kidney (IHK) and 11 with non-isolated hyperechoic kidney (NIHK). Chromosomal aneuploidies were detected in 4 of 20 patients (20%). The detection rate of pathogenic or suspected pathogenic copy number variations (CNVs) was 29% (4/14) for IHK and 37% (4/11) for NIHK. Whole exome sequencing (WES) was performed in 5 fetuses, and pathogenic genes were detected in all of them. The rate of termination of pregnancy was 56% in HEK. 21 studies including 1,178 fetuses were included in the meta-analysis. No case of abnormal chromosome karyotype or (intrauterine death)IUD was reported in fetuses with IHK. In contrast, the positive rate of karyotype in NIHK was 22% and that in HEK was 20%, with the ORs of 0.28 (95% CI 0.16-0.51) and 0.25, (95% CI 0.14-0.44), respectively. The positive rate of (chromosome microarray analysis) CMA in IHK was 59% and that in NIHK was 32%, with the ORs of 1.46 (95% CI 1.33-1.62) and 0.48 (95% CI, 0.28-0.85), respectively. The positive rate of monogenic etiologies in IHK was 31%, with the OR of 0.80 (95% CI 0.25-2.63). In IHK, the termination rate was 21% and neonatal mortality was 13%, with the ORs of 0.26 (95% CI, 0.17-0.40), 1.72 (95% CI, 1.59-1.86), and that in NIHK was 63%, 0.15 (95% CI, 0.10-0.24); 11%, 0.12 (95% CI, 0.06-0.26), respectively. The intrauterine mortality in NIHK group was 2%, with the OR of 0.02 (95% CI, 0.01-0.05). HNF1B variant has the highest incidence (26%) in IHK. Conclusion: The positive rate of karyotype was 20% in HEK and 22% in NIHK. The positive rate of CMA was 32% in NIHK and 59% in IHK. The positive rate of IHK monogenic etiologies was 31%. HNF1B gene variation is the most common cause of IHK. The overall fetal mortality rate of NIHK is significantly higher than that of IHK. The amount of amniotic fluid, kidney size and the degree of corticomedullary differentiation have a great impact on the prognosis, these indicators should be taken into consideration to guide clinical consultation and decision-making.

Correlation Analysis and Prognostic Impacts of Biological Characteristics in Elderly Patients with Acute Myeloid Leukemia.

BackgroundThe significant heterogeneity of elderly AML patients’ biological features has caused stratification difficulties and adverse prognosis. This paper did a correlation study between their genetic mutations, clinical features, and prognosis to further stratify them.Methods90 newly diagnosed elderly acute myeloid leukemia (AML) patients (aged ≥60 years) who detected genetic mutations by next-generation sequencing (NGS) were enrolled between April 2015 and March 2021 in our medical center.ResultsA total of 29 genetic mutations were identified in 82 patients among 90 cases with a frequency of 91.1%. DNMT3A, BCOR, U2AF1, and BCORL1 mutations were unevenly distributed among different FAB classifications (p < 0.05). DNMT3A, IDH2, NPM1, FLT3-ITD, ASXL1, IDH1, SRSF2, BCOR, NRAS, RUNX1, U2AF1, MPO, and WT1 mutations were distributed differently when an immunophenotype was expressed or not expressed (p<0.05). NPM1 and FLT3-ITD had higher mutation frequencies in patients with normal chromosome karyotypes than abnormal chromosome karyotypes (p<0.001, p=0.005). DNMT3A and NRAS mutations predicted lower CR rates. DNMT3A, TP53, and U2AF1 mutations were related to unfavorable OS. TET2 mutation with CD123+, CD11b+ or CD34- predicted lower CR rate. IDH2+/CD34- predicted lower CR rate. ASXL1+/CD38+ and SRSF2+/CD123- predicted shorter OS.ConclusionThe study showed specific correlations between elderly AML patients’ genetic mutations and clinical features, some of which may impact prognosis.

Analysis of parental abnormal chromosomal karyotype and subsequent live births in Chinese couples with recurrent pregnancy loss

The frequency and distribution of chromosomal abnormalities and the impact of parental chromosomal aberration on the pregnancy outcomes of couples with recurrent pregnancy loss remains controversial. 3235 RPL couples who experienced two or more miscarriages before 20 weeks were diagnosed in our tertiary referral hospital during 2008–2018 and included in the single-center retrospective cohort study covering a 10-year period. Chromosome aberration was detected in 121 (3.74%) among 3235 RPL couples which included 75 female and 46 male cases at an individual level. 101 cases were structural aberrations including balanced translocations in 46(38.0%) cases, Robertsonian translocations in 13(10.7%) cases, inversions in 42(34.7%) cases and 20(16.5%) cases were numerical aberrations. 121 carriers and 428 non-carriers were followed up for two years, 55 carriers and 229 non-carriers were subsequent pregnant after diagnosis by natural conception or intrauterine insemination. The frequency of carriers to have a health newborn was not significantly different with non-carriers (72.7% vs. 71.2%, adjusted P = 0.968). This study described the majority of carriers were balanced translocations and chromosome aberrations had a limited influence on live birth rate from the present data. The results of the study also remind us that natural conception may be also a good alternative rather than PGD (Pre-implantation Genetic Diagnosis) which is common in many other reproductive centers for such patients.

Cell-free fetal DNA testing and its correlation with prenatal indications

BackgroundThe prenatal test of cell-free fetal DNA (cffDNA) is also known as noninvasive prenatal testing (NIPT) with high sensitivity and specificity. This study is to evaluate the performance of NIPT and its clinical relevance with various clinical indications.MethodsA retrospective analysis was conducted on 14,316 pregnant women with prenatal indications, including advanced maternal age (≥35 years), maternal serum screening abnormalities, the thickened nuchal translucency (≥2.5 mm) and other ultrasound abnormalities, twin pregnancy/IVF-ET pregnancy, etc. The whole-genome sequencing (WGS) of maternal plasma cffDNA was employed in this study.ResultsA total of 189 (1.32%) positive NIPT cases were identified, and 113/189 (59.79%)cases were confirmed by invasive prenatal testing. Abnormal serological screening (53.14%) was the most common indication, followed by elderly pregnancy (23.02%). The positive prediction value for T21, T18, T13, sex chromosome abnormalities, other autosomal aneuploidy abnormalities, and CNV abnormalities were 91.84, 68.75,37.50, 66.67, 14.29, and 6.45%, respectively. The positive rate and the true positive rate of nuchal translucency (NT) thickening were the highest (4.17 and 3.33%), followed by the voluntary requirement group (3.49 and 1.90%) in the various prenatal screening indications. The cffDNA concentration was linearly correlated with gestational age (≥10 weeks) and the positive NIPT group’s Z-score values.Conclusionswhole-genome sequencing of cffDNA has extremely high sensitivity and specificity for T21, high sensitivity for T18, sex chromosome abnormalities, and T13. It also provides evidence for other abnormal chromosomal karyotypes (CNV and non-21/18/13 autosomal aneuploidy abnormalities). The cffDNA concentration is closely related to the gestational age and determines the specificity of NIPT. Our results highlight NIPT’s clinical significance, which is an effective prenatal screening tool for high-quality care of pregnancy.

Clinical Characteristics and Prognosis of Elderly Patients with Medium and High risk Myelodysplastic Syndrome

To investigate the clinical characteristics and prognosis of patients with medium and high risk myelodysplastic syndrome (MDS). 97 MDS patients above the age of 60 treated in Nanfang Hospital, Southern Medical University from February 2011 to August 2020 were enrolled. The clinical characteristics and prognosis of the MDS patients with medium risk, high risk or very high risk based on IPSS-R category were retrospectively analyzed. According to the difference of treatment regimes, the patients were divided into the transplantation group, chemotherapy group and other treatment group, and the efficacy among the patients in the 3 groups were analyzed. MDS with excess blast (MDS-EB) in the elderly patients with medium and high risk MDS were the most common, 47.4% of the patients with abnormal chromosome karyotypes, and 23.7% with complex karyotypes (≥3). 97.3% of the patients showed at least one gene mutation, and TP53 mutations were detected in nearly 20% of the patients with medium and high risk. Multivariate analysis showed that IPSS-R category and treatment regimes were the factors affecting the prognosis of elderly patients with medium and high risk MDS. The median overall survival (OS) time of the patients in the 3 groups showed significant difference (P=0.012), and the median OS of the patients in the transplantation group was significantly longer than that in the chemotherapy group and other group (P=0.003,P=0.014,respectively), while there was no significant difference in median OS between chemotherapy group and other treatment group (P=0.685). Elderly MDS patients with medium and high risk can benefit from allogeneic hematopoietic stem cell transplantation, which will prolong their OS.

The Relationship between Prenatal Diagnosis Indications and Abnormal Chromosomal Karyotypes: A Retrospective Cohort of 4646 Cases in Beijing from 2012-2019.

Chromosomal abnormalities are one of the genetic disorders caused by abnormal chromosome number or structure and can endanger multiple organs, morphology and function of the systems in the human body. This study aims to investigate the relationship between prenatal diagnosis indications and abnormal karyotypes to improve prenatal screening. The karyotype analyses were carried out on 4646 pregnant women with prenatal diagnosis indications referred to the first medical center of Chinese PLA General Hospital from 2012 to 2019. The incidence, distribution, and statistical features of chromosomal abnormality of different prenatal diagnosis indications were analyzed, and the relationships with the prenatal diagnosis indications were assessed. A total of 351 fetal chromosomal abnormalities were detected in 4646 karyotypes, with an incidence of 7.6%. The chromosomal abnormality incidence in the single indication group, two indications group, and three indications group was 5.8%, 16.1%, and 70.0%, respectively, indicating a statistically significant difference (p < 0.05). Advanced maternal age (AMA), high-risk maternal serum screening (MSS), and non-invasive prenatal DNA testing (NIPT) were the important indications for predicting abnormal karyotype. The number of prenatal diagnosis indications was highly correlated with fetal chromosomal abnormalities. The overall incidence of chromosomal abnormalities showed a tendency to increase with age. The incidence of Trisomy 21 was 3.2%, accounting for 42.5% of all chromosomal abnormalities, and the incidence tended to increase with maternal age. Prenatal karyotype analysis of pregnant women with prenatal diagnosis indications can effectively prevent the birth of defective children. AMA, MSS and NIPT were the important indications for predicting abnormal karyotype. In addition, the number of prenatal diagnosis indications is highly correlated with chromosomal abnormalities.

Application of chromosome microarray analysis in prenatal diagnosis

BackgroundTo explore the application value of chromosomal microarray analysis (CMA) in prenatal diagnosis.MethodsThe results of chromosome karyotype analysis and CMA of 477 cases undergoing amniocentesis were analyzed. The results of the no ultrasound abnormality group and the ultrasound abnormality group were compared separately. Within the ultrasound abnormality group, the results of the ultrasound structural malformation group, the ultrasound soft index abnormality group, and other ultrasound abnormality (including abnormal amniotic fluid volume and fetal growth restriction) groups were compared.ResultsAbnormal chromosome and CMA results were found in a total of 71 cases (15.88%, 71/447), which can be broken down into a total of 23 karyotype abnormalities (5.15%, 23/447), consisting of 18 cases of aneuploidy (4.03%, 18/447), 2 cases of unbalanced chromosome rearrangements (0.44%, 2/447), and 3 cases of chimerism (0.67%, 3/447); 17 cases with detection of pathogenic copy number variations (pCNVs) (3.80%, 17/447); and 31 cases of detection of clinical variants of unknown significance (VOUS) (6.93%, 31/447). CMA detected 3.8% more genetic abnormalities than karyotype analysis (in addition to the abnormalities detected simultaneously by karyotype analysis). Between the no ultrasound abnormality group and the ultrasound abnormality group, there was an extremely significant difference in the detection rate of an abnormal chromosomal karyotype (P < 0.01) and of VOUS (P < 0.01), but there was no significant difference in the detection rate of pCNV (P > 0.05). Comparing the ultrasound structural malformation group, the ultrasound soft index abnormality group, and the other ultrasound abnormality group, there were no significant differences in the detection rate of abnormal chromosomal karyotypes (P > 0.05), pCNV (P > 0.05) or VOUS (P > 0.05).ConclusionsThe detection rate of chromosomal karyotype abnormalities in prenatal diagnosis in cases with no ultrasound abnormalities was higher. For cases with fetal ultrasound structural abnormalities, when compared with traditional karyotype analysis, CMA can improve the detection rate of fetal genetic abnormalities. However, the no ultrasound abnormality group also had a high VOUS abnormality detection rate, so it is necessary to strictly define the CMA indications.

The Cytogenetic Aberrations of Lymphoplasmacytic Lymphoma/ Waldenström’s Macroglobulinemia in China

Object:Lymphoplasmacytic lymphoma/ Waldenström's macroglobulinemia (LPL/WM) is a rare B-cell proliferative malignancy characterized by immunoglobulin M monoclonal gammopathy and /or bone marrow infiltration by lymphoplasmacytic cells. Recently, there are no large-scale studies to detect the clinical features, genetic background in patients with LPL/WM in China even Asia. The aim of this study is to explore the clinical and genetic differences, observe the impact of cytogenetic abnormalities on survival and prognosis in Chinese patients. Methods:305 patients with LPL/WM admitted in our hospital from June 1998 to December 2018 were retrospectively analyzed. Baseline characteristics, laboratory detection and therapy were compared using Chi-square test and Kaplan-Meier methodology was undertaken for survival analysis. Results:The median age of 305 patients in the study was 62 years (range 32-87) and male to female ratio was 2.45:1(216/89). The most common symptoms at diagnosis were fatigue (64.9%) and bleeding (14.1%).The patients in low, intermediate and high risk group of the international prognostic scoring system for WM (ISSWM) was 17.6%, 36.5% and 45.9%,respectively.The median hemoglobin was 8.5g/dl(range 2.4-18.7). About 41.3% patients had IgM higher than 4000mg/dl. The cytogenetic abnormalities were uncommon in LPL/WM patients. The chromosomal karyotypes were successful in 194 cases, of which 20 patients showed clonal abnormalities. 12 patients had two or more chromosome abnormalities. The most common chromosome abnormalities were deletion 6/6q(25%) and Y chromosome loss (20%). The median progression-free survival (PFS) and overall survival (OS) in patients with normal and abnormal chromosome karyotypes were similar. 194 patients had FISH detection, of which 33 patients (17%) had FISH abnormalities, 9 (4.6%) patients had two kind of abnormalities. The patients with more than one cytogenetic abnormality had lower survival than just had one abnormality or normal patients. The most common aberrations were 6q deletion and trisomy 12. 17p deletion was detected in 11 patients (11/184,6.0%) and it was a poor prognostic marker of PFS and OS. Single 13q14 deletion had not impact on PFS or OS, but when companied with other cytogenetic aberration, it could worsen the PFS and OS . Besides related to survival, cytogenetic abnormal was also related to the clinical features. Conclusions:Despite the low incidence and abnormal cytogenetic detection rate of LPL/WM, the clinical and genetic features are unique in Chinese patients. The cytogenetic aberrations play an important role in predicting prognosis. Disclosures No relevant conflicts of interest to declare.

Analysis of copy number variation by sequencing in fetuses with nuchal translucency thickening.

ObjectiveCopy number variation sequencing (CNV‐seq) technique was used to analyze the genetic etiology of fetuses with increased nuchal translucency (NT).MethodsA total of 139 women with gestational 11‐14 weeks whose fetuses were detected with increased NT (NT ≥ 2.5 mm) in our hospital from July 2016 to December 2018 were selected. Fetal specimens were performed for karyotyping analysis and CNV sequencing.ResultsAccording to the nuchal translucency thickness, 2.5‐3.4, 3.5‐4.4, 4.5‐5.4, and more than 5.5 mm, the rates of chromosomal abnormalities were 22.8% (13/57), 30.8% (12/39), 42.1% (8/19), and 62.5% (15/24), respectively. There was significant difference among the incidences of chromosomal abnormalities in four groups (χ2 = 37.69, P < .01) and the incidences increased with fetal NT thickness. Among 139 cases, there were 36 cases (25.9%) with abnormal chromosome karyotypes. Meanwhile, there were 45 cases (32.3%) with abnormal CNV. In the 12 cases with abnormal CNV and normal chromosome karyotypes, there were 2 cases of pathogenic CNV, 7 cases of CNV with unknown clinical significance, and 3 cases of possibly benign CNV. There was no significant difference in CNV between pregnant women in advanced maternal age and those in normal maternal age (χ2 = 1.389, P = .239). In the fetus who showed abnormalities in NT and ultrasonography (χ2 = 5.13, P < .05) and the fetus aborted (χ2 = 113.19, P < .05), the abnormal rate of CNV was higher with statistically significant difference.ConclusionCNV‐seq combined karyotype analysis should be performed simultaneously in fetuses with increased NT, providing a basis for genetic counseling, which is of great significance for prenatal diagnosis.

Three patients with 46,X,inv(Y)(p11.2q11.2)pat/45,X and their pedigree analysis.

The present study aimed to perform chromosome examination and pedigree analysis on three patients with semen abnormality who had undergone in vitro fertilization–embryo transfer (IVF‐ET). Peripheral blood cell culture and chromosome karyotyping were performed on 4,200 individuals who had undergone chromosome examination. Among them, 155 pregnant women who had successfully conceived were subjected to amniotic cell culture and chromosome karyotyping and those with abnormal chromosome karyotype were further subjected to C‐banding and whole‐genome sequencing. Mosaicism for a 46,X,inv(Y)(p11.2q11.2)pat/45,X karyotype was identified in the probands and immediate adult male relatives. The incidence of this mosaicism in the study population was only 0.07% (3/4,200), which is reported for the first time. For the proband of pedigree A, the results of whole‐genome sequencing and other tests were normal, and the chromosome karyotype of IVF fetuses was 46,X,inv(Y)(p11.2q11.2)pat. All the male members of three pedigrees have normal phenotypes, with no features of Turner's syndrome (45,X) or hermaphroditism (45,X/46,XY), suggesting that the inverted Y chromosome is extremely unstable and particularly susceptible to loss in somatic cells. So we speculate this karyotype may be a unique type of inverted Y chromosome in somatic cells.

The utility of nuchal translucency ultrasound in identifying rare chromosomal abnormalities not detectable by cell-free DNA screening.

AbstractObjectiveTo evaluate the utility of nuchal translucency (NT) screening in the detection of rare chromosomal aneuploidies in the setting of cell‐free DNA (cfDNA).MethodsA retrospective cohort study of pregnancies screened through the California Prenatal Screening Program between March 2009 and December 2012. Karyotype analysis was the primary method of chromosomal evaluation during the study period and abnormal chromosomal karyotype results were classified by whether the abnormality would be detectable by cfDNA (nonmosaic trisomy 13, 18, 21 or sex‐chromosomal aneuploidy [SCA]). For those rare aneuploidies detectable by karyotype but not cfDNA, the number of cases that had an increased NT and the detection rate and positive predictive value (PPV) of increased NT for rare aneuploidies were determined.ResultsA total of 452 901 pregnant women had screening. There were 2572 chromosomally abnormal fetuses, of which 1922 (74.7%) had a common aneuploidy detectable by cfDNA, leaving 450 979 without T13, 18, 21. Of these, 4181 (0.93%) had an NT ≥3.0 mm. There were 649 rare aneuploidies not detectable by cfDNA. Of these, 108 (16.6%) had an NT ≥3.0 mm. The PPV of an NT ≥3.0 mm for rare aneuploidies was 2.6%. In all, 4176 fetuses need to be screened with NT to detect a rare aneuploidy.ConclusionsThe addition of NT to cfDNA screening would detect 16.6% of rare aneuploidies. Increased NT has a low PPV for rare aneuploidies and a large number of women would need NT screening to detect each affected fetus.

Therapeutic Response and Prognosis of Adult Acute Myeloid Leukemia with Chromosome Karyotype Abnormalities

To investigate the efficacy and prognosis of acute myeloid leukemia (AML) patients with chromosome karyotype abnormalities. The clinical features and treatment responses of 91 patients with AML were collected and analyzed retrospectively. The efficacy and survival rate of the AML patients with normal and abnormal chromosome karyotype were compared. Chromosome translocations and monosomal karyotypes were the main heterogeneity of AML. There was no significant difference in complete remission rate and overall response rate between the normal and abnormal karyotype groups, but the recurrence rate was higher in abnormal karyotype group. There was no significant difference in response of AML patients received the standard "3+7 regimen" and pre-excitation chemotherapy in the treatment of normal and abnormal karyotype groups. The relapse free survival time (RFS) was longer in the normal karyotype group, but there was no significant difference in overall survival time (OS). The abnormal karyotype of AML is an independent prognostic factor, monosomal karyotype shows a poor prognosis, and the recurrence rate in AML patients with monosomal karyotype is higher.

Isolation and characterization of spontaneously immortalized B-lymphocyte lines from HIV-infected patients with and without non-Hodgkin's Lymphoma.

Isolation of viable circulating tumor cells (CTC) holds the promise for improving screening, early diagnosis, and personalized treatment of lymphoma. In this study, we isolated and characterized spontaneously immortalized B‐lymphocyte (SIBC) lines from HIV‐infected patients with and without Non‐Hodgkin's Lymphoma (AIDS‐NHL). A total of 22 SIBC lines was isolated from peripheral blood mononuclear cells (PBMC) of HIV‐infected patients with (n = 40) and without (n = 77) clinically detectable NHL, but not from healthy individuals (n = 34). Of these, 8 SIBC lines named HIV‐SIBC were generated from HIV‐infected patients without AIDS‐NHL (10%, 8/77), while 14 SIBCs named AIDS‐NHL‐SIBC were from 13 of the AIDS‐NHL patients (32.5%, 13/40). Among the 14 AIDS‐NHL‐SIBCs, 12 were derived from AIDS‐NHL patients with poor prognoses (survival time less than 1 year). SIBCs displayed markers typical of memory B cells (CD3‐CD20+CD27+) with EBV infection. Moreover, AIDS‐NHL‐SIBCs were representative of CTC as evidenced by monoclonal Ig gene rearrangement, abnormal chromosomal karyotype, and the formation of xenograft tumors, while HIV‐SIBCs generated harbored some features of tumor cells, none had the capacity of xenograft tumor formation, suggesting HIV‐SIBC present the precursor of CTC. These results indicate that SIBCs is associated with poor prognosis in AIDS‐NHL patients and can be isolated from HIV‐infected patients with NHL and without NHL. This findings point to the need for further molecular characterization and functional studies of SIBCs, which may prove the value of SIBCs in the diagnosis, prognoses, and screening for NHL among HIV‐infected patients.

Prenatal diagnosis of two fetuses with renal structural anomalies caused by 17q12 deletion syndrome

Objective To analyze the prenatal clinical characteristics and genetic diagnosis of two fetuses with chromosome 17q12 deletion syndrome mainly manifested by renal structural abnormalities. Methods Clinical data of two pregnant women admitted to Peking University First Hospital in 2017 due to ultrasound indication of fetal kidney structure abnormality in the second trimester were collected. Results of fetal chromosome karyotype analysis and array-based comparative genomic hybridization (aCGH), and aCGH detection of peripheral blood in the two couples were reviewed. Results (1) In both pregnancies of case 1 and case 2, no abnormal chromosome karyotype was found. In case 2, the fetal fluorescence in situ hybridization (FISH) results showed no abnormality. (2) During the first pregnancy of case 1, there was a 1.351 Mb of single-copy deletion in chromosome 17q12 (34 817 422-36 168 104) and a 1.187 Mb of single-copy duplication in chromosome 3p26.3 (838 934-2 026 269) extracted from umbilical cord blood. Moreover, a 1.299 Mb of single copy duplication in chromosome 3p26.3 (726 645-2 026 269) extracted from maternal peripheral blood was detected. (3) DNA analysis of the umbilical cord blood of case 2 showed a 1.351 Mb of single copy deletion in 17q12. No abnormal copy number variants (CNVs) were detected in the peripheral DNA of the couple. Conclusions Invasive prenatal detection of CNVs in cases with abnormal fetal kidney ultrasound findings might help to confirm the diagnosis and guide genetic counseling. Key words: Chromosome deletion; Chromosomes, Human, Pair 17; Ultrasonography, prenatal; DNA copy number variations; Kidney; Congenital abnormalities

Effect of Expression Levels of MiRNA-132, -125, -143 and -145 on Autophagy and Apoptosis of Multiple Myeloma Cells

To investigate relationship of miRNA-132, miRNA-256, miRNA-143 and miRNA-145 level with antophagy and apoptosis of multiple mgeloma cells. Human myeloma cell line U266 and normal CD138+ plasma cells were selected and used for study and detection, the 45 cases of MM were enrolled in MM group, and 40 normal persons were sellectod in control group. The expression of miRNA-132, miRNA-125b, miRNA-143 and miRNA-145 were measured by using qPCR, the expressions of autophagy-related protein (LC3-Ⅱ, LC3-Ⅰ, P62, beclin-1) and apoptosis-related molecules (cleaved-Caspase3, cleaved-Caspase7, BCL-2, BAX) were measured by using Western blot, respectively. The rate of apoptosis was measured by using flow cytometry. The correlation of miRNA expression level with clinical-related indexes including M protein, hemoglobin, β2-MG, lactate dehydrogenase, albumin, creatinine and serum calcium was analyzed. Compared with normal plasma cells, the expression of miRNA-132 and miRNA-125b in myeloma cells increased significantly (P<0.05), and the expression of miRNA-143 and miRNA-145 decreased significantly (P<0.05), but the expression of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 increased significantly (P<0.05). The expression of P62. BAX, cleaved-Caspase3 and cleaved-Caspase7 decreased significantly (P<0.05), the BCL-2 expression increased significantly (P<0.05), but the rate of apoptosis decreased (P<0.05). After transfection with miRNA-125b mimic or miRNA-143 inhibitor by using the cationic liposomes, the LC3-Ⅱ /LC3-Ⅰ of normal plasma cells increased significantly (P<0.05), the expression of Beclin-1 significantly increased (P<0.05), the expression of P62 decreased significantly (P<0.05), and the apoptosis rate decreased (P<0.05). However, the apoptosis rate was not significantly changed after addition of the autophagic inhibitor 3-MA in the reaction system(P>0.05). The expressions of miRNA-132, miRNA-125b, miRNA-143 and miRNA-145 were significantly different between DS and ISS staging group, also between the patients with abnormal and normal chromosome karyotype (P<0.05). The miRNA-125b and miRNA-143 significantly correlated with the levels of β2-MG, albumin and hemoglobin (P<0.05). The expressions of miRNA-132, miRNA-125b, miRNA-143 and miRNA-145 in patients with multiple myeloma closely relate with the clinical characteristics. Both over-expression of miRNA-125b and down-expression of miRNA-143 inhibit the apoptosis of myeloma cells by up-regulation of autophagy.

Natural killer, natural killer T, helper and cytotoxic T cells in the decidua from recurrent spontaneous abortion with normal and abnormal chromosome karyotypes

ProblemRecurrent spontaneous abortion (RSA) is associated with immune imbalance at the maternal–fetal interface. Decidual immune cells and cytokines expressed at this interface regulate the response of the maternal immune system to the fetus. However, the populations and cytokine expression levels of these lymphocytes in miscarriage with normal and abnormal chromosome karyotypes remain unclear. MethodsWe assessed the populations and cytokine expression levels of Natural Killer (NK), Natural Killer T (NKT), Helper T (Th) and Cytotoxic T (Tc) cells in the decidua of RSA by flow cytometry and simultaneously analyzed the fetal chromosome karyotypes of these miscarriages. ResultsFlow cytometry showed no significant difference between RSA and normal pregnancy in the percentages of Th, Tc, NK, and NKT cells. Type-1 cells decreased significantly in the decidua of normal pregnancy, and NK2 and NKT2 cells increased significantly in the normal pregnancy group. We also found no difference in the lymphocyte composition and the proportion of types 1 and 2 subsets of the four lymphocytes in the decidua between RSA with abnormal chromosome karyotypes of villous trophoblasts (RSA-A) and RSA with normal chromosome karyotypes of villous trophoblasts (RSA-N), but the proportion of type-1 cells in both groups was significantly higher than that in normal pregnancy. ConclusionNo difference existed between the type-1 immune response of RSA in normal and abnormal chromosome karyotypes of villous trophoblasts.

Clinical Study of Patients with Myelodysplastic Syndrome Transformed into Acute Myeloid Leukemia

To study the biological characteristics and treatment response of patients with myelodysplastic syndrome (MDS) transformed into acute leukemia(AL). Using WHO standard method, the clinical characteristics of patients with MDS into AML were retrospectively analyzed, the related factors influencing the MDS into AML and the treatment response of patients were analyzed. Twenty-six cases (17%) of MDS were transformed into AL among 153 cases of middle and high risk MDS, all of which were AML. The median time of transformation from MDS into AML was 4 months (1-29),and these cases transformed into AML-M2, M4, M5 and M6. In these 26 cases of AML patients, the varying degrees of anemia symptom appeared, 2 cases were with marrow infiltration, 18 cases (69.2%) were with abnormal chromosome karyotype. Compared with karyotype before transformation into AML, the abnormal karyotype in 9 cases had been conversed (new karyotype or disappear once of existing karyotype). Total efficiency of individualized treatment for MDS transformed into AML was 80%. This treatment could improve the patients quality of life. Middle and high risk MDS patients are prone to be tranformed into AML. Multiple factors are involved in the transformation of MDS into AML. These patients showed the special biological characteristics and poorer prognosis. Demethylation treatment is helpful to achieve a good near-term curative effect.

Chromosomal abnormalities associated with male infertility in Baghdad Iraq

In the current study, 142 patients (109 azoospermia and 33 severoligospermia) were studied in order to explore the cytogenetic cause’s background and the hormonal study of male infertility in Baghdad Strip of Iraq. Of the 142 infertile males,14 patients showed abnormal chromosomal karyotypes corresponding to a frequency of 9.85% (14/142), the occurrence of chromosomal abnormalities was only confined to the azoospermia patient group. Patients with abnormal karyotypes represented 12.84% (14/109) of the azoospermia patients. Nine had a 47, XXY karyotype of Klinefelter's syndrome [47XY;64.28% (9/14)], [47XY+mar;14.28% (2/14)], [46XY,del13(p12) and (del21(p12);7.14% (1/14)], [46XY,tra(5;12, -6); 7.14% (1/14)] and one with chromosomal instability that showed multiple mosaic karyotypes 7.14% (1/14). The hormonal levels of nine patients with Klinefelter's syndrome (KFS) were diagnosed in the present study, and the results showed elevated FSH and LH concentrations compared with control. While serum testosterone values were below the control.

Effectiveness of high-dose i.v. immunoglobulin therapy for pregnant women with aspirin-heparin-resistant secondary antiphospholipid syndrome.

PurposeThis study aimed to assess the efficacy of high‐dose i.v. immunoglobulin (HIVIg) therapy in pregnant women with antiphospholipid syndrome (APS) secondary to systemic lupus erythematosus with a history of pregnancy failure, despite receiving low‐dose aspirin plus unfractionated heparin therapy, of which condition being designated as “aspirin–heparin‐resistant APS” (AHRAPS).MethodsThe HIVIg therapy (20 g/d, 5 days) was performed for the pregnancies of five women with AHRAPS.ResultsFive of the eight pregnancies ended in live births. The gestational ages of delivery in four of the five pregnancies were extended, compared with previous pregnancies. The HIVIg therapy was considered to be successful for these four pregnancies. Excluding one pregnancy that ended in miscarriage with an abnormal chromosome karyotype of the villi, the HIVIg therapy was considered to be successful in four (57.1%) of the seven pregnancies of the women with AHRAPS. Although all the live newborns were prematurely delivered, no adverse effect of the HIVIg therapy was observed.ConclusionsThe HIVIg therapy might be beneficial as an immune modifier for pregnant women with AHRAPS. However, the precise indication of which women with AHRAPS who should receive HIVIg therapy remains unknown.