Publications by authors named "Andrea Vaags"
Article Synopsis
- Genetic testing for hereditary cancer in Ontario has evolved due to new risk gene discoveries and advancements in technology, requiring updates to testing eligibility criteria.
- Expert working groups created a standardized 76-cancer-gene panel and updated guidelines to ensure coordinated access to testing across the province.
- After implementing these changes, 10,564 hereditary cancer testing panels were conducted in the first year, with a mutation detection rate of 12.2%.
Article Synopsis
- The document outlines key considerations and recommendations for Canadian clinical laboratories involved in next-generation sequencing (NGS)-based tumor testing for ovarian cancers, covering pre-analytical, analytical, and post-analytical aspects.
- It was created by the Canadian College of Medical Geneticists’ somatic BRCA Ad Hoc Working Group and incorporates feedback from CCMG members before receiving board approval.
- The guidelines serve as a resource for laboratories but do not encompass all necessary information for the effective validation and use of NGS in this context.
Introduction: Genotyping circulating tumor DNA (ctDNA) is a promising noninvasive clinical tool to identify the T790M resistance mutation in patients with advanced NSCLC with resistance to EGFR inhibitors. To facilitate standardization and clinical adoption of ctDNA testing across Canada, we developed a 2-phase multicenter study to standardize T790M mutation detection using plasma ctDNA testing.
Methods: In phase 1, commercial reference standards were distributed to participating clinical laboratories, to use their existing platforms for mutation detection.
Article Synopsis
- The study focused on resolving conflicting interpretations of genetic variants among Canadian clinical laboratories through the Canadian Open Genetics Repository (COGR).
- Using the Franklin Genoox platform, laboratories could upload their variant classifications and received reports highlighting discrepancies for reassessment.
- The results showed a significant reduction in discordant variants after reassessment, supporting the effectiveness of COGR in promoting standardized interpretations and enhancing the quality of genetic testing in clinical practices.
Article Synopsis
- The study evaluates the effectiveness of four diagnostic protocols for detecting alpha-1-antitrypsin deficiency across different Canadian laboratories from 2011 to 2018.
- Among the protocols, ON-CD had the highest detection rate for pathogenic variants, but also reported more undefined molecular variants and likely benign variants compared to the others.
- The research concludes that comprehensive detection strategies covering the entire SERPINA1 coding sequence are better at identifying both pathogenic and non-pathogenic variants.
Article Synopsis
- Copy-number variations (CNVs) are linked to neurodevelopmental disorders and can manifest in various ways; this study focused on the ELP4-PAX6 locus in a large sample of individuals with neurodevelopmental conditions compared to healthy controls.
- The research identified several cases with ELP4 deletions and associated conditions such as language impairment, developmental delay, autism, and epilepsy, indicating a potential connection between these deletions and neurodevelopmental issues.
- A significant excess of CNVs at ELP4 was found in patients compared to controls, suggesting that ELP4 deletions may be pathogenic and increase the risk of a range of neurodevelopmental disorders.
Article Synopsis
- Synaptic function is crucial for brain activities, and studying patients missing specific synaptic proteins helps deepen our understanding of this function.
- The research highlights a rare disease linked to the absence of the synaptic protein CNKSR2, affecting individuals aged 6 to 62, resulting in various neurological issues.
- Key symptoms of CNKSR2 deficiency include intellectual disability, attention difficulties, and sudden loss of language skills following early childhood epilepsy, shedding light on its role in broader neurological disorders.
Article Synopsis
- The CHD2 protein is important for gene regulation and has been linked to critical functions in embryonic development, tumor suppression, and neurodevelopmental disorders due to its role in chromatin remodeling and histone acetylation.!* -
- A multicenter study identified patients with deletions in the CHD2 gene, revealing common clinical features like developmental delay, intellectual disability, and epilepsy, with no distinctive facial characteristics or brain malformations.!* -
- Findings indicate that CHD2 haploinsufficiency is likely a cause of various neurodevelopmental issues, demonstrating variability in symptoms among individuals, and underscore the need for further exploration of its complete phenotypic spectrum.!*
Article Synopsis
- The HOX11/TLX1 gene is linked to T cell acute lymphoblastic leukemia (T-ALL) due to a specific chromosome translocation, causing its inappropriate expression in T cells.
- Research on mice with altered TLX1 expression and DNA repair deficiencies showed that these mice developed T-ALL and acute myeloid leukemia (AML) more quickly than normal ones.
- The study found that thymocytes in these mice had increased proliferation and issues with cell cycle regulation, highlighting the combined effects of TLX1 dysregulation and faulty DNA repair in leukemia development.
Article Synopsis
- Rare copy number variants (CNVs) affecting ASTN2 and TRIM32 were found in individuals with neurodevelopmental disorders (NDDs), highlighting their possible link to conditions like autism and ADHD.
- A large study screened nearly 90,000 individuals, uncovering 46 deletions and 12 duplications of ASTN2, particularly enriched in NDD subjects compared to controls.
- The research shows that certain ASTN2 deletions are more common in males and suggests astrotactins play a significant role in brain development and associated psychopathology.
Article Synopsis
- The study aimed to evaluate the safety and effectiveness of eNOS-transfected bone marrow cells (BMCs) in improving left ventricular (LV) function after a myocardial infarction (MI) in a pig model.
- Fifteen female Yorkshire pigs were treated with either eNOS-BMCs, non-transfected BMCs, or a control (PBS), with cardiac function assessed using MRI at two time points: one week and six weeks post-MI.
- Results indicated that both types of cell therapy were safe and led to better improvements in LV function than the control group, with eNOS-BMCs showing some advantages in reducing infarct mass and LV remodeling, suggesting further research is needed for similar human applications.
Article Synopsis
- - The GPHN gene encodes for gephyrin, a protein essential for organizing glycine and GABA receptors at inhibitory synapses in the brain, which is linked to neurodevelopmental disorders like autism and schizophrenia.
- - Research shows that abnormalities in GPHN mRNA, potentially caused by stress during epilepsy, may lead to seizures and other related conditions.
- - The study identifies six individuals with neurodevelopmental diagnoses who have unique deletions in the GPHN gene, suggesting these deletions may impact gephyrin's function and contribute to various disorders.
Article Synopsis
- The study investigates the impact of deletions in the 16q24.2 region of DNA, linking them to conditions like autism spectrum disorder (ASD), intellectual disability (ID), and congenital renal anomalies.
- Out of 35 individuals analyzed, many had deletions near the known disease-associated genes FOXF1 and ANKRD11, with a significant number diagnosed with ASD or ID, and some with hydronephrosis.
- The findings suggest that the 16q24.2 region is crucial for understanding these conditions, indicating a need for further research on specific genes like C16orf95 and ZCCHC14 that show potential links to disease development.
Article Synopsis
- The human neurexin gene family includes NRXN1, NRXN2, and NRXN3, which are crucial for the development and function of synapses in the brain.
- In autism spectrum disorder (ASD) and other neurodevelopmental conditions, variations in the NRXN1 and NRXN2 genes have been linked to the disorder, while this report focuses on rare deletions in the NRXN3 gene.
- The study highlights four ASD cases with NRXN3 deletions, showcasing the complexity of genetic factors in autism, including issues of penetrance and expressivity among family members with and without formal ASD diagnoses.
Article Synopsis
- In utero hematopoietic cell transplantation is a technique used to treat diseases in fetuses by injecting cells into the yolk sac, though optimal methods for this procedure are not well-defined.
- Researchers tested different doses of cells in canine fetuses at different gestational ages (day 25 and 35) to study survival rates and how well cells migrate into the fetus.
- The results indicated that while the survival rates were similar, higher cell doses increased fetal mortality, but successfully injected cells could migrate to key hematopoietic tissues in the fetuses, confirming the yolk sac method as a safe and effective approach.
Article Synopsis
- The study investigates how MRI can track bone marrow progenitor cells (BMCs) after they are delivered via the intracoronary route post-myocardial infarction (MI).
- In an experiment with 11 pigs, MRI was used to observe the cells' location over six weeks, revealing that the cell signal in the infarct border persisted but decreased in intensity over time.
- The results showed BMC treatment significantly reduced infarct volume and improved the heart's ejection fraction, demonstrating the potential of MRI to monitor cell delivery and its therapeutic effects in cardiac repair.
Article Synopsis
- Embryonic stem cells (ESCs) can remain undifferentiated and have the ability to develop into various cell types from the three germ layers, making them valuable for research and potential medical applications.
- Researchers successfully derived permanent canine ESC lines from early-stage embryos, which show similarities to human ESCs in terms of specific protein expression and cell characteristics.
- These canine ESCs also demonstrated the ability to form different cell types in lab settings and teratomas in living organisms, presenting opportunities to investigate ESC-based treatments for human diseases using large animal models.
Article Synopsis
- * Researchers are exploring the use of HIV TAT, a protein that helps transport other proteins across membranes, to improve enzyme delivery.
- * Fusion constructs of glucocerebrosidase and TAT were produced in Sf9 cells, showing successful expression, with modified TAT constructs yielding better results than wild-type TAT.