Genomic Copy Number Variants in CML Patients With the Philadelphia Chromosome (Ph+): An Update

BackgroundSubmicroscopic segmental imbalances detected by array-comparative genomic hybridization (array-CGH) were discovered to be common in chronic myeloid leukemia (CML) patients with t(9;22) as the sole chromosomal anomaly. To confirm the findings of the previous study and expand the investigation, additional CML patients with t(9;22) as the sole chromosomal anomaly were recruited and copy number variants (CNVs) were searched for.MethodsKaryotyping tests were performed on 106 CML patients during January 2010–September 2019 in our Genetics Laboratory. Eighty-four (79.2%) patients had the Philadelphia (Ph) chromosome as the sole chromosomal anomaly. Only 49(58.3%) of these 84 patients had sufficient marrow or leukemia blood materials to additionally be included in the array-CGH analysis. Fluorescence in situ hybridization (FISH) was carried out to confirm the genes covered by the deleted or duplicated regions of the CNVs.Results11(22.4%) out of the 49 patients were found to have one to three somatic segmental somatic segmental (CNVs), including fourteen deletions and three duplications. The common region associated with deletions was on 9q33.3-34.12. Identified in five (45.5%) of the 11 positive patients with segmental CNVs, the deletions ranged from 106 kb to 4.1 Mb in size. Two (18.2%) cases had a deletion in the ABL1-BCR fusion gene on der (9), while three (27.3%) cases had a deletion in the ASS1 gene. The remaining CNVs were randomly distributed on different autosomes.ConclusionSubtle genomic CNVs are relatively common in CML patients without cytogenetically visible additional chromosomal aberrations (ACAs). Long-term studies investigating the potential impact on patient prognosis and treatment outcome is underway.

Prevalence of associated extracardiac anomalies in prenatally diagnosed congenital heart diseases

Objective To investigate the prevalence of extracardiac anomalies (ECA) in prenatally diagnosed congenital heart diseases (CHD), and to provide more information for counseling of women with prenatally diagnosed fetal CHD. Methods This was a retrospective cohort study of 791 cases of fetal CHD diagnosed by prenatal ultrasound from January 2005 to April 2018. Associated ECAs included extracardiac structural malformation (ECM), chromosomal anomaly, and 22q11.2 microdeletion. CHD was classified into 10 groups according to a modified anatomic and clinical classification of congenital heart defects. Results The overall prevalence of ECA in our CHD cohort was 28.6% (226/791): ECM, 25.3%; chromosomal anomaly, 11.7%; and 22q11.2 microdeletion, 5.5%. For those with ECM, ventricular septal defect (VSD) had the highest prevalence (34.5%), followed by anomalies of atrioventricular junctions and valves (28.8%) and heterotaxy (26.9%). For those with chromosomal anomaly, anomalies of atrioventricular junctions and valves had the highest prevalence (37.5%), followed by anomalies of atria and interatrial communications (25.0%) and VSD (22.9%). 22q11.2 microdeletion was detected only in those with anomalies of extrapericardial arterial trunks (14.3%) or ventricular outflow tracts (6.4%). Conclusion ECM, chromosomal anomaly, and 22q11.2 microdeletion have different prevalence according to the type of CHD.

Assessment of second-trimester amniocentesis cases: 10-year experience of a tertiary center

Objective The aim is to contribute to the literature by carrying out retrospective analysis of the cases who underwent amniocentesis in our clinic and sharing our relevant experience. Methods A total of 632 cases who underwent amniocentesis in the second trimester were included in our study. The cases’ demographic characteristics, weeks of gestation, amniocentesis indications, procedure-related complications, culture success, cytogenetic results, and the results and indications of the cases found to have chromosomal anomalies were evaluated. Chromosomal anomalies, their complications, culture failure rates and most common amniocentesis indications were reported. The results of the cases with chromosomal anomalies were presented as numerical and structural anomalies. Results The mean age of all cases included in our study was 33.7±6.8 years, and their mean weeks of gestation were 17.5±1.0 weeks. The rate of the cases found to have chromosomal anomaly by amniocentesis was 22.4%, the culture failure rate was 2.1%, and complication rate was 0.5%. The most common amniocentesis indications and the amniocentesis indications in cases found to have chromosomal anomaly were the same, and they were as following respectively: combined test being high risk, triple screening test being high risk and presence of anomaly in the ultrasonography (USG). The rate of detecting chromosomal anomaly was higher in the cases who had multiple indications and underwent amniocentesis. Conclusion Although USG and serum screening tests are used commonly for prenatal diagnosis, invasive tests such as amniocentesis are needed for the final diagnosis in patients with high risk. We concluded that amniocentesis is more important for prenatal diagnosis in cases who are under risk of having multiple chromosomal anomalies in the screening tests.

Pattern of congenital heart disease among Egyptian children: a 3-year retrospective study

Background Congenital heart disease (CHD) is a multifactorial birth defect which has variable demographic characteristics among children in different geographical areas. This study aimed to detect the distribution of demographic data, perinatal risk factors, types, age, and mode of presentation of CHD among Egyptian children. Results The medical records of 1005 patients were included. They were 545 males (54%) and 462 females (46%) with a ratio of 1.2:1. Acyanotic CHD was encountered in 79.2%. Isolated ventricular septal defect and tetralogy of Fallot were the most common acyanotic and cyanotic lesions, respectively. The majority was diagnosed within the first year of life (86.7%) and was born to young mothers (91.3%). The accidental discovery of a murmur was the most frequent presentation (35%). Heart failure was detected in 44%, audible murmurs in 74.4%, maternal illnesses in 54%, consanguinity in 44.6%, prematurity in 19.3%, assisted reproduction in 11.7%, family history of CHD in 9.2%, abortions in 7.1%, and extracardiac anomalies in 3.6% of the studied population. Down syndrome (DS) was the most commonly occurring chromosomal anomaly, and the atrioventricular septal defect was the most characteristic cardiac lesion found among them. Conclusions There is no sex predilection among Egyptian children with CHD. Most of the cases are diagnosed in early infancy. Accidental discovery of a murmur is the most common mode of presentation. A variety of predisposing risk factors are abundant in the Egyptian population. DS is the most common chromosomal anomaly linked to CHD. Establishment of a national medical birth registry containing all information about all births in Egypt is needed for adequate surveillance and monitoring of perinatal health problems and congenital birth defects so that preventive measures can be early implemented. Proper and detailed data collection should be fulfilled in the medical records of every single patient.

Fetal Ultrasound Image Evaluation of Chromosomal Anomaly Detection and Classification Using Conditional Rooted Neural Network (CRNN)

In this work, a computerized scheme of Chromosomal anomaly recognition and classification of Chromosomal abnormality such as Trisomy (T) T-13, T-18 and T-21 (Patau, Edwards and Down syndrome) based on Conditionally Rooted neural network (CRNN) with wavelet Filter. CRNN is used to estimate the chromosomal anomaly features separation from fetal provisions. The clear template of feature estimation from the first-trimester fetus of ultrasound images will be used to train the CRNN Neural Network. The software has successfully identified and classified the region of chromosomal anomaly. The evaluations show that our CRNN technique can attain good denoising and classification performance in comparison with existing methods. In this experiment, the results indicate that our proposed method can detect and classify the trisomy factors measurement from the US image regions precisely and robustly against speckle noise. The classification of Fetus US image datasets was done using CRNN classifier, and the accuracy of classification was found to be Highly efficient resolution for Chromosomal anomaly detection.