ORIGINAL ARTICLES

MULTIPLE CONGENITAL ANOMALY CAUSED BY AN EXTRA AUTOSOME

A balanced gene complement is crucial for proper cell function. Aneuploidy, the condition of having an imbalanced chromosome set, alters the stoichiometry of gene copy numbers and protein complexes and has dramatic consequences at the cellular and organismal levels. In humans, aneuploidy is associated with different pathological conditions including cancer, microcephaly, mental retardation, miscarriages, and aging. Over the last century, Drosophila has provided a valuable system for studying the consequences of systemic aneuploidies. More recently, it has contributed to the identification and molecular dissection of aneuploidy-induced cellular behaviors and their impact at the tissue and organismal levels. In this perspective, we review this active field of research, first by comparing knowledge from yeast, mouse, and human cells, then by highlighting the contributions of Drosophila. The aim of these discussions was to further our understanding of the functional interplay between aneuploidy, cell physiology, and tissue homeostasis in human development and disease.

Chromosome copy number imbalances, otherwise known as aneuploidies, are a common but poorly understood feature of cancer. Here, we describe recent advances in both detecting and manipulating aneuploidies that have greatly advanced our ability to study their role in tumorigenesis. In particular, new clustered regularly interspaced short palindromic repeats (CRISPR)-based techniques have been developed that allow the creation of isogenic cell lines with specific chromosomal changes, thereby facilitating experiments in genetically controlled backgrounds to uncover the consequences of aneuploidy. These approaches provide increasing evidence that aneuploidy is a key driver of cancer development and enable the identification of multiple dosage-sensitive genes encoded on aneuploid chromosomes. Consequently, measuring aneuploidy may inform clinical prognosis, while treatment strategies that target aneuploidy could represent a novel method to counter malignant growth.

CENP-A is an essential histone variant that replaces the canonical H3 at the centromeres and marks these regions epigenetically. The CENP-A nucleosome is the specific building block of centromeric chromatin, and it is recognized by CENP-C and CENP-N, two components of the constitutive centromere-associated network (CCAN), the first protein layer of the kinetochore. Recent proposals of the yeast and human (h)CCAN structures position the assembly on exposed DNA, suggesting an elusive spatiotemporal recognition. We summarize the data on the structural organization of the CENP-A nucleosome and the binding of CENP-C and CENP-N. The latter posits an apparent contradiction in engaging the CENP-A nucleosome versus the CCAN. We propose a reconciliatory model for the assembly of CCAN on centromeric chromatin.

and background: Patau syndrome or trisomy 13 is a clinically severe condition; 85 percent of patients die before reaching the age of one year, and the majority of children die before reaching the age of six months.

This report discusses a case of a male infant, two days old diagnosed with Patau syndrome. After birth, his APGAR score was satisfactory. The initial clinical examination revealed cleft palate, cleft lip, and congenital clubfoot. A pansystolic murmur was heard at the left sternal border. The patient was managed according and was referred to a surgeon for pulmonary binding, PDA ligation, VSD closure, and repair of ASA with disbanding of the pulmonary artery.

Studies have reported that patients with Patau syndrome present with cleft lip and palate, congenital heart defects, omphalocele, and holoprosencephaly. we also discovered dysmorphic characteristics such as the cleft palate and cleft lip, as well as serious congenital cardiac abnormalities. In addition, up to 80% of patients have been documented to have cardiac abnormalities, with patent ductus arteriosus, atrial septal defect, and ventricular septal defect.

Patau syndrome is the third most common trisomy found in infants. The clinical manifestation of Patau syndrome includes cleft palate, cleft lip, limb impairments, and congenital heart problems. Despite the fact that early diagnosis and management prognosis is poor for patients suffering from Patau syndrome. Genetic counseling may be beneficial not just for increasing awareness of the diagnosis and its implications.

To examine the retinal vascular findings on widefield fluorescein angiography (FA) in the fellow eyes of patients with unilateral persistent fetal vasculature (PFV).

Retrospective case series.

Consecutive patients with unilateral PFV evaluated by a single physician at an academic medical center from February 1, 2011, to November 30, 2018.

Clinical and demographic information, including age, gender, race, ethnicity, affected eye, subtype, stalk origin, complications on presentation, length of follow-up, and examination findings, was reviewed using the electronic medical record. Fluorescein angiograms of the affected and fellow eyes were reviewed by 2 authors for characteristic retinal vascular abnormalities. Agreement between the authors’ scores was analyzed using Cohen's Kappa.

Fluorescein angiography abnormalities, including peripheral vessel avascularity, aberrant circumferential vessels, terminal supernumerary branching, regional capillary dropout, terminal bulbing, abnormal choroidal flush, abnormal vessel straightening, and peripheral vessel leakage or dilation.

Inclusion criteria were met by 41 patients. The average age at initial visit was 10.0 months. The average length of follow-up was 36.4 months. Abnormalities on FA were seen in 31 (75.6%) fellow eyes: peripheral vessel avascularity in 27.5 (67.1%), aberrant circumferential vessels in 20 (48.8%), terminal supernumerary branching in 17 (41.5%), regional capillary dropout in 9 (22.0%), terminal bulbing in 6 (14.6%), abnormal choroidal flush in 3.5 (8.5%), and abnormal vessel straightening and peripheral vessel leakage in 2.5 (6.1%). Statistical analysis disclosed an overall observed agreement of 93.4% among the raters (κ = 0.84, P < 0.0001).

Retinal vascular abnormalities seen in patients with unilateral PFV were present in the majority of fellow eyes. This suggests that unilateral PFV may in fact be a bilateral, asymmetric process, but the clinical significance of these subtle findings is not known.

From karyotyping to sequencing, the development and improvement of technologies that allow to study the human genome at greater resolution have revealed the extent to which it varies. A major contributor to human genomic variation is structural variation that shapes the architecture of the genome. Genomic rearrangements derived from such architecture and that can result in genetic disorders due to the disruption or alteration of the dosage of genes are known as genomic disorders. The transition from classic cytogenetic techniques to DNA next-generation sequencing (NGS) in research and the clinic has invigorated the study of these disorders. As NGS technologies evolve, it is our ability to detect and understand smaller and cryptic inherited and de novo, rare disease-associated genomic rearrangements, leading to major advances in current genomic testing, bioinformatic algorithms, and population studies of structural variation. This chapter aims to review the progress in the study of genomic disorders, including the applied genomic technologies, their capabilities and pitfalls, as well as the collective efforts by the genetics community to generate datasets and guidelines to more accurately interpret structural variants in health and disease.