Lipoblastomas (LPBs) are rare benign neoplasms derived from embryonal adipose that occur predominantly in childhood. LPBs typically present with numeric or structural rearrangements of chromosome 8, the majority of which involve the pleomorphic adenoma gene 1 (PLAG1) proto-oncogene on chromosome 8q12. Here, we report on a LPB case on which showed evidence of chromothripsis. This is the second reported case of chromothripsis in LPB.

The discovery of potential disease-causing genes can aid medical progress. The post-genomic era has made this a more difficult task. Modern high-throughput methods have not solved the problem of identifying disease genes. Conventional methods cannot be used to investigate many rare or lethal diseases. Monitoring gene expression values in different samples using microarray technology is one of the best and most accurate ways to identify disease-causing genes. One of the most recent advances in experimental molecular biology is microarrays, which allow researchers to simultaneously monitor the expression levels of thousands of genes. Statistical analysis of microarray data might aid gene discovery by revealing pathways related to the target gene and facilitating identification of candidate genes. Systems biology, an interdisciplinary approach, has emerged as a crucial analytic tool with the potential to reveal previously unidentified causes and consequences of human illness. Genetic, environmental, immunological, or neurological factors have been implicated in the developing complex disorders like cancer. Because of this, it is important to approach the study of such disease from a novel perspective. The system biology approach allows us to rapidly identify disease-causing genes and assess their viability as therapeutic targets. This chapter demonstrates systems biology approaches to identify candidate genes using public database. Oral squamous cell carcinoma (OSCC) is used as a model disease to show how systems biology can be used successfully to identify and prioritize disease genes.

Chlamydia trachomatis infection is a major cause of sexually transmitted diseases and adverse pregnancy outcomes such as recurrent spontaneous abortion (RSA). Micro-RNAs (miRNAs) have been known to be upregulated/downregulated in various reproductive-associated diseases such as ectopic pregnancy, preterm birth and pre-eclampsia. However, there is paucity of literature on miRNA profile in C. trachomatis-infected RSA. The present study aimed to determine the profile of serum miRNAs followed by their validation in C. trachomatis-infected RSA and to find target genes involved in biological pathways. Non-heparinized blood and first void urine were collected from 30 non-pregnant women with RSA and 30 non-pregnant women with ≥2 successful deliveries (controls) attending Department of Obstetrics and Gynaecology, Safdarjung hospital, New Delhi, India. C. trachomatis detection was done in urine by PCR and chlamydial load was determined by quantitative real-time PCR (qRT-PCR). miRNA expression was studied by microarray analysis followed by in vitro validation by qRT-PCR. Analysis of target genes/pathways was characterized in silico. 06 RSA patients were infected with C. trachomatis, while chlamydial load was found to be 6000-12,000 copies/ml. 110 circulating miRNAs were expressed differentially in infected RSA patients compared with controls. Of these, 16 were overexpressed and 94 downregulated. 06 differentially expressed circulating miRNAs were selected to validate the microarray results. qRT-PCR data confirmed the reliability of the microarray results: miR-4443, -5100, -7975 showed statistically significant upregulation, while miR-6808-5p, -3148, -6727-5p were significantly downregulated in infected RSA patients versus controls. Chlamydial load was positively correlated with these upregulated miRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that target genes of miRNAs in RSA are involved in AMPK, Akt and mTOR signaling pathways. Overall results indicate that differentially expressed circulating miRNAs are involved in pathogenesis of C. trachomatis-associated RSA and have the potential to be used as biomarkers for predicting RSA.

Hexagonal grid layouts are advantageous in microarray technology; however, hexagonal grids appear in many fields, especially given the rise of new nanostructures and metamaterials, leading to the need for image analysis on such structures. This work proposes a shock-filter-based approach driven by mathematical morphology for the segmentation of image objects disposed in a hexagonal grid. The original image is decomposed into a pair of rectangular grids, such that their superposition generates the initial image. Within each rectangular grid, the shock-filters are once again used to confine the foreground information for each image object into an area of interest. The proposed methodology was successfully applied for microarray spot segmentation, whereas its character of generality is underlined by the segmentation results obtained for two other types of hexagonal grid layouts. Considering the segmentation accuracy through specific quality measures for microarray images, such as the mean absolute error and the coefficient of variation, high correlations of our computed spot intensity features with the annotated reference values were found, indicating the reliability of the proposed approach. Moreover, taking into account that the shock-filter PDE formalism is targeting the one-dimensional luminance profile function, the computational complexity to determine the grid is minimized. The order of growth for the computational complexity of our approach is at least one order of magnitude lower when compared with state-of-the-art microarray segmentation approaches, ranging from classical to machine learning ones.

This paper presents a consensus-based approach that incorporates three microarray and three RNA-Seq methods for unbiased and integrative identification of differentially expressed genes (DEGs) as potential biomarkers for critical disease(s). The proposed method performs satisfactorily on two microarray datasets (GSE20347 and GSE23400) and one RNA-Seq dataset (GSE130078) for esophageal squamous cell carcinoma (ESCC). Based on the input dataset, our framework employs specific DE methods to detect DEGs independently. A consensus based function that first considers DEGs common to all three methods for further downstream analysis has been introduced. The consensus function employs other parameters to overcome information loss. Differential co-expression (DCE) and preservation analysis of DEGs facilitates the study of behavioral changes in interactions among DEGs under normal and diseased circumstances. Considering hub genes in biologically relevant modules and most GO and pathway enriched DEGs as candidates for potential biomarkers of ESCC, we perform further validation through biological analysis as well as literature evidence. We have identified 25 DEGs that have strong biological relevance to their respective datasets and have previous literature establishing them as potential biomarkers for ESCC. We have further identified 8 additional DEGs as probable potential biomarkers for ESCC, but recommend further in-depth analysis.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders which are etiologically heterogeneous. Chromosomal microarray is now recommended as the first-tier clinical diagnostic test for ASD. We performed chromosomal microarray in 16 Thai patients with ASD using an Illumina HumanCytoSNP-12 v2.1 array and found one case with uniparental disomy (UPD) of chromosome 15. Methylation-specific PCR showed abnormal methylation of the maternal SNRPN allele. Haplotype analysis revealed that the patient had received both chromosomes 15 from his father. These results were consistent with Angelman syndrome. However, his clinical features had no clinical significance for classic Angelman syndrome. He had first presented at the pediatric clinic with no speech, poor social interaction skills and repetitive behaviors consistent with ASD based on the DSM-IV criteria at 2 years of age and later confirmed by ADOS at 5 years of age. He was strikingly overweight but had no dysmorphic facies, seizures nor ataxia and was diagnosed as non-syndromic ASD, a diagnosis which was believed until at 10 years of age, his DNA was included for analysis in this current cohort study. Our findings suggest that ASD patients with unknown etiology should be considered for methylation-specific PCR testing for Angelman syndrome where chromosomal microarray is not available. In the study, we also review the clinical features of Angelman syndrome caused by UPD and the frequency of ASD in individuals with Angelman syndrome.

T-cell acute lymphoblastic leukemia is a subtype of acute lymphoblastic leukemia, one of the most common childhood neoplasms. Hypodiploidy is a chromosome abnormality with fewer than 45 chromosomes and is associated with unsatisfactory clinical outcomes in acute lymphoblastic leukemia.
We report clinical and genetic findings of a 14-year-old male with T-cell acute lymphoblastic leukemia with low-hypodiploidy. The medical history included neck pain for a month, facial nerve palsy on the right side for 6 days, fever, drowsiness, and weakness for 3 days, vomiting, diarrhea for 1 day. The physical examination presented features of hypovolemia, palsy of the facial nerve on the right side, enlarged lymph nodes, hepatosplenomegaly, sore throat, and petechiae of the skin. Radiological images indicated lesions of different organs. Bone marrow biopsy confirmed precursor T-ALL. In the FISH tests, KMT2A and BCR/ABL1 rearrangements were not observed. GTG banding revealed 3 cell clones, which confirmed the hypodiploidy. Multiplex RT-qPCR was performed. STIL/TAL1 (del1p32) gene rearrangement was found in the blast cells. Additional tests were performed using the CytoScan HD microarray technique. Molecular karyotype did not reveal hypodiploidy, but identified other abnormalities such as duplication of chromosomal regions: 4q25q35.2, 6p23.3p11.1 and 8p23.3q24.21, and the loss of heterozygosity of short arm chromosome 9. In two regions of the chromosome biallelic deletions were found at 9p21.3, including the CDKN2A, CDKN2B, IFNA1, MTAP genes and at 10q23.31, containing PTEN. The child died 9 days after diagnosis.
Bone marrow biopsy, GTG banding, FISH techniques, and molecular karyotyping were used to make an accurate diagnosis. This case documents a rapid progression of the disease and unfavorable results of T-cell acute lymphoblastic leukemia with hypodiploidy.

Neuroblastoma is the most common cancer in infants younger than 12 months of age, occurring with an incidence of 1 in 100,000 children. The clinical outcome of neuroblastoma ranges from spontaneous regression to treatment-resistant progression and/or metastasis, and accounts for 8-10% of childhood cancer deaths. Segmental chromosomal aberrations, as well as MYCN and ALK amplification, are among factors contributing to an unfavorable genomic profile and high-risk disease classification. Here, we describe a 5-year-old male who presented with a large right renal neuroblastoma tumor having lung and liver metastases. Fluorescence in situ hybridization analysis indicated the presence of >20 copies of the 5\' region of the ALK gene in 26% of cells examined. Subsequent copy number assessment did not confirm ALK amplification, but revealed a gain of exons 2-5 of ALK, consistent with increased copy number for the 5\' region of the ALK gene. Subsequent array analysis showed the presence of other unfavorable prognostic genomic features, including segmental gain of the 17q region and amplification of the long arm of chromosome 12 harboring CDK4 and MDM2, both reported to be poor prognostic indicators in patients with atypical clinical features in neuroblastoma. Taken together, this report illustrates the importance of careful interpretation of aberrant FISH findings and subsequent use of orthogonal methods to clarify the presence of genomic alterations to successfully determine potential treatment targets.

16p11.2 microdeletion is a known chromosomal anomaly associated mainly with neurocognitive developmental delay, predisposition to obesity, and variable dysmorphism. Although this deletion is relatively rare among the general population, it is one of the serious known genetic aetiologies of obesity and autism spectrum disorder.
This study presents three cases of deletions within the 16p11.2 region. Every child had mild variable craniofacial abnormalities, hand or foot anomalies and developmental and language delays. The first proband had obesity, epilepsy, moderate intellectual disability, aphasia, motor delay, hyperinsulinism, and café au lait spots. The second proband suffered from cardiac, pulmonary, and haematological problems. The third proband had motor and language delays, bronchial asthma, and umbilical hernia. Although each patient presented some features of the syndrome, the children differed in terms of their clinical pictures. Genetic diagnosis of 16p11.2 microdeletion syndrome was made in children at different ages based on multiplex ligation probe-dependent amplification analysis and/or microarray methods.
Our reports allow us to analyse and better understand the biology of 16p11.2 microdeletion throughout development. However, the variability of presented cases supports the alternate conclusion to this presented in available literature regarding 16p11.2 deletion, as we observed no direct cause-and-effect genotype/phenotype relationships. The reported cases indicate the key role of the interdisciplinary approach in 16p11.2 deletion diagnostics. The care of patients with this anomaly is based on regular health assessment and adjustment of nervous system development therapy.

The objective of our paper is to underline the importance of assessing microarray genetic analysis for the detection of chromosomal abnormalities in rare cases such as left atrial isomerism, mostly in the context of antenatally detected syndromes. We present the case of a 26-year-old primipara, at 26 weeks of gestation, with prior first trimester normal anomaly scan, who presented in our department accusing lower abdominal pain. An anomaly ultrasound examination of the fetus revealed cardiomegaly with increased size of the right atrium, non-visualization of the atrial septum or the foramen ovale, malalignment of the three-vessel view, location of the superior vena cava above the two-vessel view, slight pericardial effusion, and no interruption of the inferior vena cava nor presence of azygos vein being noted. Associated extracardiac abnormalities, such as small kidneys at the level of the iliac fossa, micrognathia, dolichocephaly with hypoplasia of the cerebellum, increased nuchal fold, and reduced fetal movements were also reported. A diagnostic amniocentesis was performed, and, while the conventional rapid prenatal diagnostic test of the multiplex quantitative fluorescent polymerase chain reaction (PCR) came as normal, the microarray analysis (ChAS, NCBI Built 37 hg 19, detection of microdeletions or microduplications larger than 100 kb) revealed two chromosomal abnormalities: a 22.84 Mb loss of genetic material in the 18q21.31-18q23 chromosomal region and a gain of 22.31 Mb of genetic material in the 20p13-20p11.21 chromosomal region. After the termination of pregnancy, a necropsy of the fetus was performed, confirming heterotaxy syndrome with a common atrium, no atrial septum, superior vena cava draining medianly, and pulmonary veins that drained into the lower segment of the left atrium due to an anatomically enlarged single common atrium. The extracardiac findings consisted of two bilobar lungs, dysmorphic facies, low-set ears, nuchal fold edema, and small kidneys located in the iliac fossa. These findings are conclusive evidence that left atrial isomerism is a more complex syndrome. The genetic tests of the parents did not reveal any translocations of chromosomes 18 and 20 when the Fluorescent in situ Hybridization (FISH) analysis was assessed. The antenatal detection of corroboration between different structural abnormalities using serial ultrasound examinations and cardiac abnormalities, together with the detection of the affected chromosomes, improves the genetic counseling regarding the prognosis of the fetus and the recurrence rate of the condition for siblings.