Life Sciences Commons^™

Fungal Empyema Thoracis, A Rare But An Emerging Entity: A Retrospective Case Series From Pakistan, Nousheen Iqbal, Akbar Shoukat Ali, Aqusa Zahid, Kauser Jabeen, Muhammad Irfan

Section of Pulmonary & Critical Care

Background and objective: Fungal empyema is a rare entity which is associated with high mortality. It is mostly seen in immune-compromised hosts. However, there is limited data available on fungal empyema from developing countries regarding risk factors, treatment, and outcome. This study was conducted to determine the risk factors, clinical features, treatment, and outcome of fungal empyema.
Methods: A retrospective observational study was performed on proven fungal empyema cases, admitted at Aga Khan University Hospital, Karachi, Pakistan during January 2018 to May 2021. We excluded all those patients with polymicrobial bacterial and fungal empyema or with negative pleural fluid cultures. …

27-Hydroxycholesterol And Dna Damage Repair: Implication In Prostate Cancer, Gloria Cecilia Galvan, Nadine Friedrich, Sanjay Das, James Daniels, Sara Pollan, Shweta Dambal, Ryusuke Suzuki, Sergio Sanders, Sungyong You, Hisashi Tanaka, Yeon-Joo Lee, Wei Yuan, Johann De Bono, Irina Vasilevskaya, Karen Knudsen, Michael Freeman, Stephen Freedland

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: We previously reported that cholesterol homeostasis in prostate cancer (PC) is regulated by 27-hydroxycholesterol (27HC) and that CYP27A1, the enzyme that converts cholesterol to 27HC, is frequently lost in PCs. We observed that restoring the CYP27A1/27HC axis inhibited PC growth. In this study, we investigated the mechanism of 27HC-mediated anti-PC effects.

METHODS: We employed in vitro models and human transcriptomics data to investigate 27HC mechanism of action in PC. LNCaP (AR+) and DU145 (AR-) cells were treated with 27HC or vehicle. Transcriptome profiling was performed using the Affymetrix GeneChip™ microarray system. Differential expression was determined, and gene set enrichment …

Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

ncreased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE₂/EP2 feedforward loop, …

Regulation Of Mirnas In Obesity And Diabetes, Eva Maher, Ava O'Meara, Cathy Brougham

SURE Journal: Science Undergraduate Research Experience Journal

Introduction: The prevalence of obesity and obesity-related secondary disorders has increased dramatically in recent years. Dysregulated microRNA (miRNA) expression has been linked to the development of obesity and its associated disorders. Adipose derived stem cells (ADSCs) are promising cell models of obesity, obesity-related inflammation and diabetes. Furthermore, miRNA expression profiles have emerged as promising targets for the novel treatment of diseases such as obesity. In order to enhance miRNA-based therapies, the miRNA expression profile of obesity and its related disorders must be monitored to further understand the underlying mechanisms of obesity and to identify novel targets.

Aim: The aim of …

The Potential Of Stem Cell Therapy In Multiple Sclerosis Treatment: A Review, Sorina Amarculesei, Ava O'Meara Cushen, Cathy Brougham

SURE Journal: Science Undergraduate Research Experience Journal

Multiple Sclerosis is an autoimmune and neurodegenerative disease of the central nervous system. There are currently 2.8 million people living with Multiple Sclerosis worldwide, including 9000 people in Ireland, with a prevalence of 193 per 100,000 people. Symptoms of Multiple Sclerosis include sensory loss, fatigue, cognitive dysfunction, spasticity, depression, optic neuritis, gait ataxia, diplopia, and loss of bladder control. Currently, there is no standardised treatment or cure for Multiple Sclerosis with many strategies focusing on symptoms. Stem cells have emerged as promising approaches for Multiple Sclerosis therapeutics. Clinical trials primarily focus on mesenchymal stem cell-based therapies for Multiple Sclerosis. Furthermore, …

Tiny But Mighty, An Exploration Of Microbes And Plants As Sources Of Small Novel Bioactive Compounds Against Invasive Mycoses., Hannah Mai Peacock, James Anthony O'Connor

SURE Journal: Science Undergraduate Research Experience Journal

Despite the high mortality rate involved with invasive cerebral mycoses, there is a relative lack of research available around antifungals capable of crossing the blood brain barrier.

In this study the metabolites of four plants (Crocus vernus, Miniature Narcissus (daffodil), Osmanthus delavayi and Taraxacum officinale (common dandelion)) and two bacteria (Lacticaseibacillus paracasei and Staphylococcus epidermidis) were extracted and assayed for antifungal activity against Candida albicans and Saccharomyces cerevisiae. Thin layer chromatography and bioautography were then employed to assess the activity of the constituent components of sources showing antifungal activity.

Metabolites of S.epidermidis, and extracts …

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …

Allergic Bronchopulmonary Aspergillosis: Radiological And Microbiological Profile Of Patients Presented In An Outpatient Pulmonary Clinic In A Developing Country, Nousheen Iqbal, Muhammad Irfan, Mustafa Bin Ali Zubairi, Maaha Ayub, Safia Awan, Kauser Jabeen, Ali Bin Sarwar Zubairi

Section of Pulmonary & Critical Care

There is limited data available about allergic bronchopulmonary aspergillosis (ABPA) in Pakistan. The aim of the study was to describe the radiological and microbiological profile of ABPA patients presenting to the outpatient pulmonary clinic of a tertiary care hospital in Karachi, Pakistan. A retrospective study was conducted on ABPA patients who presented to the pulmonary outpatient clinic at Aga Khan University Hospital, Karachi, Pakistan, from January 2017 to December 2019. Data was collected on microbiology and radiology features on predesigned proforma. A total of 7759 asthmatic patients presented at the outpatient pulmonology clinic during the study period. Of the 245 …

Impacts Of Environmental Stressors On Native South Dakota Amphibian Physiology And Survival, Danielle Jean Galvin

Dissertations and Theses

Amphibian populations around the world are declining, with some of the most likely drivers behind these declines including emerging infectious diseases and environmental contaminants. To address major gaps in the current literature, I sought to evaluate the effect of two major environmental stressors on various aspects of amphibian physiology: emerging infectious diseases and environmental contaminants. Emerging infectious diseases of amphibians include fungal, viral, and parasitic pathogens which have expanded in host range, either geographically or in competent host species. Environmental contaminants include chemicals which may be naturally occurring in the environment, or which may be introduced to the environment, often …

Interpretable Mechanistic And Machine Learning Models For Pre-Dicting Cardiac Remodeling From Biochemical And Biomechanical Features, Anamul Haque

All Dissertations

Biochemical and biomechanical signals drive cardiac remodeling, resulting in altered heart physiology and the precursor for several cardiac diseases, the leading cause of death for most racial groups in the USA. Reversing cardiac remodeling requires medication and device-assisted treatment such as Cardiac Resynchronization Therapy (CRT), but current interventions produce highly variable responses from patient to patient. Mechanistic modeling and Machine learning (ML) approaches have the functionality to aid diagnosis and therapy selection using various input features. Moreover, 'Interpretable' machine learning methods have helped make machine learning models fairer and more suited for clinical application. The overarching objective of this doctoral …

Human-Bat Interactions In A Disease Emergence Hotspot: Implications For Human Health And Bat Conservation, Reilly Tempest Jackson

Graduate Theses and Dissertations

Bats are an ecologically important taxon that can host zoonotic pathogens. Globally, many bat species are synanthropic and live closely with humans, often roosting in man-made structures. The spatial overlap between humans and bats creates opportunities for human-bat contact, which can lead to human exposure to bat-borne pathogens and conflicts that cause bat mortality. Despite this risk, little is known about the drivers and characteristics of these human-bat interactions in buildings and work is needed to understand this aspect of the wildlife-urban interface. In Chapter I, I present a literature review that identifies the geographic and taxonomic trends in reported …

Neutralizing Antibodies Against Ebv Gp42 Show Potent In Vivo Protection And Define Novel Epitopes, Qian Wu, Ling Zhong, Dongmei Wei, Wanlin Zhang, Junping Hong, Yinfeng Kang, Kaiyun Chen, Yang Huang, Qingbing Zheng, Miao Xu, Mu-Sheng Zeng, Yi-Xin Zeng, Ningshao Xia, Qinjian Zhao, Claude Krummenacher, Yixin Chen, Xiao Zhang

Faculty Scholarship for the College of Science & Mathematics

Epstein-Barr virus (EBV) is the first reported human oncogenic virus and infects more than 95% of the human population worldwide. EBV latent infection in B lymphocytes is essential for viral persistence. Glycoprotein gp42 is an indispensable member of the triggering complex for EBV entry into B cells. The C-type lectin domain (CTLD) of gp42 plays a key role in receptor binding and is the major target of neutralizing antibodies. Here, we isolated two rabbit antibodies, 1A7 and 6G7, targeting gp42 CTLD with potent neutralizing activity against B cell infection. Antibody 6G7 efficiently protects humanized mice from lethal EBV challenge and …

Relative Hepatotoxocity, Carcinogenicity, And Toxicogenomics Of Select Dehydropyrrolizidine Alkaloids In Mice, Michael J. Clayton

All Graduate Theses and Dissertations, Fall 2023 to Present

Dehydropyrrolizidine alkaloids are arguably the most important plant derived toxins in terms of impact on human and animal health. Dehydropyrrolizidine alkaloids are a large group of chemically related compounds found in 3% of flowering plants worldwide. Human exposure occurs from ingestion of herbal products including teas supplements or contaminated grain. Animals are exposed through contaminated feed or grazing. There are at least 350 identified toxic PAs, from more than 6,000 plants. The toxins primarily cause liver damage, but some are proven to cause cancer. Indidvidual dehydropyrrolizidine alkaloids vary in their toxic effects. Riddelliine is the only dehydropyrrolizidine alkaloid with extensive …

Diabetes-Associated Hyperglycemia Causes Rapid-Onset Ocular Surface Damage, Judy Weng, Christopher Ross, Jacob Baker, Saleh Alfuraih, Kiumars Shamloo, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose: The metabolic alterations due to chronic hyperglycemia are well-known to cause diabetes-associated complications. Short-term hyperglycemia has also been shown to cause many acute changes, including hemodynamic alterations and osmotic, oxidative, and inflammatory stress. The present study was designed to investigate whether diabetes-associated hyperglycemia can cause rapid-onset detrimental effects on the tear film, goblet cells, and glycocalyx and can lead to activation of an inflammatory cascade or cellular stress response in the cornea.

Methods: Mouse models of type 1 and type 2 diabetes were used. Tear film volume, goblet cell number, and corneal glycocalyx area were measured on …

Special Issue: Hunger, Nutrition, And Health, Susan Rice

Journal of Food Law & Policy

Everyday millions of Americans face barriers to accessing food, housing, and other supports–––making the impossible decision of whether to put food on the table or cover other essential needs. Food insecurity and diet-related diseases, such as heart disease and diabetes, affect people of all ages and in all communities. It was for this reason that the Biden-Harris Administration hosted the White House Conference on Hunger, Nutrition, and Health in September 2022. As the President said at the Conference, “No child should go to bed hungry. No parent should die of a disease that can be prevented.” It will require all …

An Investigation Of Mitigation Measures On The Spread Of Covid-19 In A College Classroom Using Agent-Based Modeling, Saharsh Talwar, Anne E. Yust

Spora: A Journal of Biomathematics

In this manuscript, we describe the process of using agent-based modeling in NetLogo to create a simulation of COVID-19 spread in a traditional college classroom. The model allows for an evaluation of different preventative measures implemented by the University of Pittsburgh, including the cohort classroom attendance model, mask and vaccine mandates, contact tracing, and classroom sanitation. Through the use of the model's interactive interface, the impact of adjusting specific measures by the institution could be visualized, providing a valuable tool for combating diseases that spread through droplet transmission.

Untargeted Metabolomics Analysis On Kidney Tissues From Mice Reveals Potential Hypoxia Biomarkers, Muhammad Imran Sajid, Francisco J. Nunez, Farideh Amirrad, Moom Rahman Roosan, Tom Vojtko, Scott Mcculloch, Amal Alachkar, Surya M. Nauli

Pharmacy Faculty Articles and Research

Chronic hypoxia may have a huge impact on the cardiovascular and renal systems. Advancements in microscopy, metabolomics, and bioinformatics provide opportunities to identify new biomarkers. In this study, we aimed at elucidating the metabolic alterations in kidney tissues induced by chronic hypoxia using untargeted metabolomic analyses. Reverse phase ultrahigh performance liquid chromatography-mass spectroscopy/mass spectroscopy (RP–UPLC–MS/MS) and hydrophilic interaction liquid chromatography (HILIC)–UPLC–MS/MS methods with positive and negative ion mode electrospray ionization were used for metabolic profiling. The metabolomic profiling revealed an increase in metabolites related to carnitine synthesis and purine metabolism. Additionally, there was a notable increase in bilirubin. Heme, N-acetyl-L-aspartic …

Assessing Copd Care Quality In A Rural Ontario Primary Care Clinic: A Retrospective Chart Review, Daniel Henke

Electronic Thesis and Dissertation Repository

Background: Primary chronic obstructive pulmonary disease (COPD) care may be worse in rural versus more urban environments.

Purpose: To evaluate the quality of COPD care in a rural Ontario primary care clinic.

Methods: A 12-month retrospective chart review study was conducted between June 2022 and January 2023 at a Goderich, Ontario primary care clinic. Electronic medical records (EMRs) were randomly selected for inclusion. Baseline sociodemographic (e.g., occupation) and health (e.g., smoking status) characteristics were extracted as well as information regarding COPD care received (i.e., Health Quality Ontario [HQO] Quality Standard [QS] indicators; n=33. The primary study outcome was overall proportion …

Novel Treatments For Pxe: Targeting The Systemic And Local Drivers Of Ectopic Calcification, Ida Joely Jacobs, Qiaoli Li

Department of Biochemistry and Molecular Biology Faculty Papers

Pseudoxanthoma elasticum (PXE) is a heritable multisystem ectopic calcification disorder. The gene responsible for PXE, ABCC6, encodes ABCC6, a hepatic efflux transporter regulating extracellular inorganic pyrophosphate (PPi), a potent endogenous calcification inhibitor. Recent studies demonstrated that in addition to the deficiency of plasma PPi, the activated DDR/PARP signaling in calcified tissues provides an additional possible mechanism of ectopic calcification in PXE. This study examined the effects of etidronate (ETD), a stable PPi analog, and its combination with minocycline (Mino), a potent inhibitor of DDR/PARP, on ectopic calcification in an Abcc6-/- mouse model of PXE. Abcc6-/- mice, at 4 weeks of …

Sars-Cov-2: Tale Of A Microscopic Murderer, Josiah P. Garner

Quest

Independent Study

Research in progress for BIOL1406: Biology for Science Majors I

Faculty Mentor: Amina Tassa, Ph.D.

I am delighted to introduce Josiah Garner’s “SARS-CoV-2: Tale of a Microscopic Murderer.” This independent study assignment explores the impact of a novel, deadly, and worldwide virus. The assignment also examines the fast development of vaccines to control the spread and reduce the symptoms of the virus.

Josiah’s paper focuses on the early history of the emergence of COVID-19, the world response, and vaccine development. He demonstrates critical thinking skills and effectively utilizes various research methods to obtain and communicate his information. Josiah …

Using Noninvasive Calibrated Cuff Plethysmography To Observe The Effects Of Cold-Water Immersion On Arterial Compliance, Rita M. Grigorian

Master's Theses

As the prevalence of cardiovascular diseases continues to exponentially grow in populations across the globe, the necessity of determining underlying factors, effective methods of diagnoses, and universally available preventive measures also grows. Early detection of endothelial dysfunction, a proven precursor of cardiovascular diseases, can be extremely impactful in encouraging preventative measures and early intervention before medical conditions become chronic. In recent years, ice plunging, a form of cryotherapy involving full body immersion in cold water, has gained popularity within circles of fitness and health practitioners, gaining the interest of people of all backgrounds. Certain parallels observed between the human physiological …

The Role Of Non-Coding Rnas In Myelodysplastic Neoplasms, Vasileios Georgoulis, Epameinondas Koumpis, Eleftheria Hatzimichael

Computational Medicine Center Faculty Papers

Myelodysplastic syndromes or neoplasms (MDS) are a heterogeneous group of myeloid clonal disorders characterized by peripheral blood cytopenias, blood and marrow cell dysplasia, and increased risk of evolution to acute myeloid leukemia (AML). Non-coding RNAs, especially microRNAs and long non-coding RNAs, serve as regulators of normal and malignant hematopoiesis and have been implicated in carcinogenesis. This review presents a comprehensive summary of the biology and role of non-coding RNAs, including the less studied circRNA, siRNA, piRNA, and snoRNA as potential prognostic and/or predictive biomarkers or therapeutic targets in MDS.

Understanding An Inflammatory Pathway In Diabetic Retinopathy, Reanna R. Rodriguez

Research Symposium

Diabetic Retinopathy (DR) is the leading cause of blindness in the U.S. However, not much is known of its molecular pathway and how it attributes to increases in inflammatory response in the eye. One avenue we will investigate is the transforming growth factor beta (TGFB) signaling pathway and its effect of vascular endothelial growth factor (VEGF) secretion and cell viability. VEGF is the hallmark that exacerbates DR progression in prolonged diabetes. Some major concern that have arisen are the underlying effects of oxidants and antioxidants in elevating VEGF secretion in diabetes. In attempt to learn more, we evaluated how an …

Human Ipsc Derived Cardiomyocyte Model Reveals The Transcriptomic Bases Of Covid-19 Associated Myocardial Injury, Kashish Kumar, Satish Kumar, Erica De Leon, Joanne E. Curran, Sarah Williams-Blangero, John Blangero

Research Symposium

Background: Multi-organ complications have been the hallmark of severe COVID-19; cardiac injuries were reported in 20% to 30% of hospitalized COVID-19 patients, although the disease etiology remains poorly understood. This study leveraged genome-wide RNA-sequence data generated using induced pluripotent stem cell (iPSC) differentiated cardiomyocytes (CMs) and in vitro modeling of SARS-CoV-2 infection in CMs, to understand the molecular mechanisms of COVID-19 myocardial injuries for novel diagnostic and therapeutic development.

Methods: Raw RNA-sequence data sets, GSE165242 and GSE150392 were aligned to human genome assembly GRCh38 and gene expressions were quantified. Differentially expressed (DE) genes between experimental groups were identified using moderated …

Hpv Imprints In Western India: The Overlooked Criteria For Cancer Profiling, Ashi R. Thobias, Jayendra B. Patel, Prabhudas P. Patel

Research Symposium

Background: In India, HPV infection detection for cancer-typing has been largely evaded. Especially, data on prevalence of HPV types other than the highly prevalent HPV 16 and 18 are lacking, particularly from the western region. Thus, present study aimed to evaluate prevalence of HPV strains in three most prevailing cancers in India i.e. cervical, oral and oropharyngeal cancer.

Materials & methods: DNA was isolated from tissue samples of 400 cervical cancer cases, 127 oral cancer cases and 75 oropharyngeal cancer cases and endpoint PCR was performed using degenerative primers MY 09/11, GP 5+/6+ and CP I/II. TS-PCR was conducted to …

A Natural Near-Infrared Fluorescent Probe For Cancer Cell Imaging, Benilde E. Adriano, Nycol M. Cotto, Neeraj Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

Research Symposium

Background: Rio Grande Valley (RGV) suffers from a high prevalence of certain cancers and lack the resources for accurate early diagnosis. Near-infrared (NIR) fluorescence-based imaging is a noteworthy and safer strategy for cancer detection compared to radiological imaging. There are several NIR dyes including indocyanine green (ICG) and its analogues that allow high-resolution and deep tissue imaging. However, these dyes possess some drawbacks, namely photo instability, toxicity, poor water solubility, and short half-lives. Chlorophyll (Chl) is a natural dietary and biocompatible NIR fluorescent substance which has the potential to serve as a cancer NIR imaging candidate. Hence, we aim to …

Erk Required For Lipopolysaccharide-Induced Tlr4 Internalization In Macrophages, Sara M. Reyna, Phoebe Fang-Mei Chang

Research Symposium

Background: Insulin resistance is associated with low circulating levels of lipopolysaccharide (LPS). Binding of LPS to Toll like receptor 4 (TLR4) leads to the internalization and trafficking of TLR4 resulting in activation of downstream signaling pathways. TLR4 internalization in macrophages leads to the activation of pro-inflammatory signaling pathways and production of factors linked to the development of insulin resistance. The extracellular signal-regulated kinase 1 and 2 (ERK1 and 2) are activated downstream of TLR4 and are associated with insulin resistance. We hypothesized that ERK1 and ERK2 regulate TLR4 internalization in macrophages when exposed to LPS.

Methods: We examined whether inhibition …

Understanding The Resources, Barriers, Facilitators And Interests About Aging And Dementia Research Of Community Members From The Rio Grande Valley, Karla Daniela Lopez Lorenzo, Rosa V. Pirela Mavarez, Gabriela Osuna, Kendra Stine, Nahalie Chacon De Alvarez, Noe Garza, Gladys E. Maestre

Research Symposium

Background: One of ten people aged 65 develops Alzheimer’s Disease and it is one of the sixth-leading cause of death in the United States. The Rio Grande Valley (RGV) is mostly constituted by Hispanic/Latinos (93%), a population that has a 1.5X increased risk of AD onset. Nevertheless, there are not enough resources to support people living with dementia and their care partners. This study will leverage research efforts deployed by the RGV Alzheimer’s Disease Resource Center for Minority Aging Research to understand the social representations about the resources, barriers, facilitators, and interests of the RGV community about dementia and Alzheimer’s …

Cell-Based Experimental Evidence To The Anti-Covid-19 Potential Of Ashwagandha And Honeybee Propolis Ingredients, Renu Wadhwa, Durai Sundar, Yoshiyuki Ishida, Keiji Terao, Sunil C. Kaul

Research Symposium

Background: The COVID-19 pandemic emerged in December 2019 by a novel strain of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has led to new endeavours in repurposing of existing drugs, anti-COVID-19 vaccine and drug development. Natural products, due to their general safety and wider availability, have attracted research and public attention. In this study, we report anti-COVID potential of compounds from honeybee propolis and Ayurvedic herb, Ashwagandha. Effect of active ingredients was studied on human cell surface receptors (ACE-2:Angiotensin Converting Enzyme-2/Spike protein and TMPRSS2:Transmembrane Protease Serine 2), critical for virus infection and virus main protease (Mpro, essential for virus replication), …

Repurposing Normal Chromosomal Microarray Data To Harbor Genetic Insights Into Congenital Heart Disease, Nephi Walton, Hoang Nguyen, Sara Procknow, Darren Johnson, Alexander Anzelmi, Patrick Jay

Department of Medicine Faculty Papers

About 15% of congenital heart disease (CHD) patients have a known pathogenic copy number variant. The majority of their chromosomal microarray (CMA) tests are deemed normal. Diagnostic interpretation typically ignores microdeletions smaller than 100 kb. We hypothesized that unreported microdeletions are enriched for CHD genes. We analyzed "normal" CMAs of 1762 patients who were evaluated at a pediatric referral center, of which 319 (18%) had CHD. Using CMAs from monozygotic twins or replicates from the same individual, we established a size threshold based on probe count for the reproducible detection of small microdeletions. Genes in the microdeletions were sequentially filtered …