Medical Specialties Commons^™

Burden Of Rare Deleterious Variants In Wnt Signaling Genes Among 511 Myelomeningocele Patients, Luke Hebert, Paul Hillman, Craig Baker, Michael Brown, Allison Ashley-Koch, James E Hixson, Alanna C Morrison, Hope Northrup, Kit Sing Au

Faculty, Staff and Student Publications

Genes in the noncanonical WNT signaling pathway controlling planar cell polarity have been linked to the neural tube defect myelomeningocele. We hypothesized that some genes in the WNT signaling network have a higher mutational burden in myelomeningocele subjects than in reference subjects in gnomAD. Exome sequencing data from 511 myelomeningocele subjects was obtained in-house and data from 29,940 ethnically matched subjects was provided by version 2 of the publicly available Genome Aggregation Database. To compare mutational burden, we collapsed rare deleterious variants across each of 523 human WNT signaling genes in case and reference populations. Ten WNT signaling genes were …

Perioperative Acute Kidney Injury, Sam D Gumbert, Felix Kork, Maisie L Jackson, Naveen Vanga, Semhar J Ghebremichael, Christy Y Wang, Holger K Eltzschig

Faculty, Staff and Students Publications

Perioperative organ injury is among the leading causes of morbidity and mortality of surgical patients. Among different types of perioperative organ injury, acute kidney injury occurs particularly frequently and has an exceptionally detrimental effect on surgical outcomes. Currently, acute kidney injury is most commonly diagnosed by assessing increases in serum creatinine concentration or decreased urine output. Recently, novel biomarkers have become a focus of translational research for improving timely detection and prognosis for acute kidney injury. However, specificity and timing of biomarker release continue to present challenges to their integration into existing diagnostic regimens. Despite many clinical trials using various …

Single-Nuclei Rna-Seq On Human Retinal Tissue Provides Improved Transcriptome Profiling, Qingnan Liang, Rachayata Dharmat, Leah Owen, Akbar Shakoor, Yumei Li, Sangbae Kim, Albert Vitale, Ivana Kim, Denise Morgan, Shaoheng Liang, Nathaniel Wu, Ken Chen, Margaret M Deangelis, Rui Chen

Faculty, Staff and Students Publications

Single-cell RNA-seq is a powerful tool in decoding the heterogeneity in complex tissues by generating transcriptomic profiles of the individual cell. Here, we report a single-nuclei RNA-seq (snRNA-seq) transcriptomic study on human retinal tissue, which is composed of multiple cell types with distinct functions. Six samples from three healthy donors are profiled and high-quality RNA-seq data is obtained for 5873 single nuclei. All major retinal cell types are observed and marker genes for each cell type are identified. The gene expression of the macular and peripheral retina is compared to each other at cell-type level. Furthermore, our dataset shows an …

Msto1 Mutations Cause Mtdna Depletion, Manifesting As Muscular Dystrophy With Cerebellar Involvement., S Donkervoort, R Sabouny, P Yun, L Gauquelin, K R Chao, Y Hu, I Al Khatib, A Töpf, P Mohassel, B B Cummings, R Kaur, D Saade, S A Moore, L B Waddell, M A Farrar, J K Goodrich, P Uapinyoying, S H S Chan, A Javed, M E Leach, P Karachunski, J Dalton, L Medne, A Harper, C Thompson, Isabelle Thiffault, S Specht, R E Lamont, Carol J. Saunders, H Racher, F P Bernier, D Mowat, N Witting, J Vissing, R Hanson, Keith A. Coffman, Meagan K. Hainlen, J S Parboosingh, A Carnevale, G Yoon, R E Schnur, Care4rare Canada Consortium, K M Boycott, J K Mah, V Straub, A Reghan Foley, A M Innes, C G Bönnemann, T E Shutt

Manuscripts, Articles, Book Chapters and Other Papers

MSTO1 encodes a cytosolic mitochondrial fusion protein, misato homolog 1 or MSTO1. While the full genotype-phenotype spectrum remains to be explored, pathogenic variants in MSTO1 have recently been reported in a small number of patients presenting with a phenotype of cerebellar ataxia, congenital muscle involvement with histologic findings ranging from myopathic to dystrophic and pigmentary retinopathy. The proposed underlying pathogenic mechanism of MSTO1-related disease is suggestive of impaired mitochondrial fusion secondary to a loss of function of MSTO1. Disorders of mitochondrial fusion and fission have been shown to also lead to mitochondrial DNA (mtDNA) depletion, linking them to the mtDNA …

Genetic Screening For Breast Cancer In The Primary Care Setting, Michael Nick Gomez

Doctor of Nursing Practice

The purpose of this project was to increase adherence to the U.S. Preventive Services Task Force and National Comprehensive Cancer Network guidelines for breast cancer screening and genetic testing. Screening for breast cancer risk factors including genetic testing helps reduce the incidence of breast cancer. A protocol was developed based on national clinical guidelines to increase screening and genetic testing for breast cancer. Provider responsibilities included screening all patients 18 years of age and older for risks factors of breast cancer, referring patients with a significant risk based on the screening for genetic testing and providing referrals for genetic counseling …

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

Dissertations and Theses (Open Access)

Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal …

A Systematic Comparison Of Lipopolymers For Sirna Delivery To Multiple Breast Cancer Cell Lines: In Vitro Studies, Hamidreza Montazeri Aliabadi, Remant Bahadur Kc, Emira Bousoik, Ashley Barbarino, Bindu Thapa, Melissa Coyle, Parvin Mahdipoor, Hasan Uludağ

Pharmacy Faculty Articles and Research

Small interfering RNA (siRNA) therapy is a promising approach for treatment of a wide range of cancers, including breast cancers that display variable phenotypic features. To explore the general utility of siRNA therapy to control aberrant expression of genes in breast cancer, we conducted a detailed analysis of siRNA delivery and silencing response in vitro in 6 separate breast cancer cell models (MDA-MB-231, MDA-MB-231-KRas-CRM, MCF-7, AU565, MDA-MB-435 and MDA-MB-468 cells). Using lipopolymers for siRNA complexation and delivery, we found a large variation in siRNA delivery efficiency depending on the specific lipopolymer used for siRNA complexation and delivery. Some lipopolymers were …

Nearly Complete Genome Sequences Of 17 Enterovirus D68 Strains From Kansas City, Missouri, 2018, Suman B. Pakala, Yi Tan, Ferdaus Hassan, Annie Mai, Robert H. Markowitz, Meghan H. Shilts, Seesandra V. Rajagopala, Rangaraj Selvarangan, Suman R. Das

Manuscripts, Articles, Book Chapters and Other Papers

Here, we report 17 nearly complete genome sequences of enterovirus D68 (EV-D68) isolated from Kansas City, MO, in 2018. Phylogenetic analysis suggests that these strains belong to subclade B3, similar to the ones that caused the 2016 epidemics in the United States but different from the 2014 outbreak B1 strains.

Acute Diagnosis Of Wilson’S Disease In A Teenage Patient, Sarah Irvin, Ryan Mccarthy

Marshall Journal of Medicine

Wilson’s Disease, a rare autosomal recessive genetic disease, is caused by a mutation in the ATP7B enzyme gene. Without this enzyme, copper builds up in the brain, liver, and cornea causing a multitude of symptoms. It is important to consider Wilson’s disease because the prognosis is dependent on timely diagnosis. This is an interesting case of a 19-year-old male who presented with suicidal thoughts and rapid weight loss. After many months and an extensive work-up, Wilson’s Disease was diagnosed. Due to his rapid decline, he was transferred to a larger university healthcare center where he is currently enrolled in clinical …

Programmed Death Pathway Inhibition: Emerging Therapeutic Options For Treatment Of Advanced Or Refractory Cancers, Katherine Elsass, Morgan Homan, Jana Randolph, Brendan Rasor, David Kinder

Pharmacy and Wellness Review

The programmed death-1 (PD-1) pathway has a significant role in the promotion of immune tolerance. The PD-1 receptor ligands are normally expressed on various inactive immune cells. When cancer cells express these ligands, they are able to interact with active T and B lymphocytes to induce this tolerance. Nivolumab and pembrolizumab are two recently approved agents that act to disrupt this binding and facilitate an immune response against cancer cells. Numerous trials, including KEYNOTE-002 and CheckMate 063, have demonstrated the superior safety and efficacy of these drugs in patients with advanced or refractory cancers. Initially approved for the treatment of …

Overview Of Kalydeco® (Ivacaftor) For Treatment Of Cystic Fibrosis, Andrew Skouby, Kayti Kintner, Kimberly Loughlin, Emily Blum, Michael Rush

Pharmacy and Wellness Review

Cystic fibrosis (CF) is a genetic disease associated with specific gene mutations that presents with pulmonary inflammation and frequent lung infections, exocrine pancreatic insufficiency, altered sweat composition and declining lung function. Ivacaftor (Kalydeco®) was approved for treatment of cystic fibrosis in patients 6 years of age and older with a G551D mutation on the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a CFTR potentiator and does not work in patients with a mutation of the F508del. Efficacy has been demonstrated in several trials with a primary outcome of improved FEV1, improvements in pulmonary exacerbations, patient-reported decrease in respiratory …

Ado-Trastuzumab Emtansine For Her2 Positive Breast Cancer, Kimberly Baucher, Taylor Beale, Maria Laikos, Eric Stack, Mary Ellen Hethcox

Pharmacy and Wellness Review

No abstract provided.

The Impact Of Pharmacogenomics On Chemotherapeutic Drug Development And Use, Lara Long, Amy Pasternak, Ellen Hazelet, David Kisor

Pharmacy and Wellness Review

Cancer therapy is largely dependent on general treatment guidelines, and patients undergoing chemotherapy often experience treatment failure with standard drugs. The development of individualized drug therapy through pharmacogenomics has the potential to enhance chemotherapy regimen selection and improve patient outcomes. Antineoplastic agents such as cetuximab and trastuzumab are effective in treating cancers possessing specific genetic biomarker characteristics. Patients need to undergo genetic testing before these agents are administered to ensure appropriate use. Cetuximab has been shown to improve outcomes in metastatic colorectal cancers and head and neck squamous cell carcinomas positive for EGFR. Trastuzumab has shown benefit in human epidermal …

Predicting Premature Birth Risk With Cfrna, Jason Lin, Jonathan Marin, John Santerre

SMU Data Science Review

Identifying which genes are early indicators for preterm births using cell-free ribonucleic acid (cfRNA) from non-invasive blood tests provided by pregnant women can improve prenatal care. Currently, there are no medical tests for early detection of preterm birth risk in routine checkups for pregnant women. Recent studies have shown potential genes that can predict preterm birth. Machine learning techniques are utilized to see if the Area Under the Curve (AUC) can be improved upon when evaluating the prediction accuracy for chosen genes sequences and concentrations. Using cell-free RNA data from non-invasive blood tests in conjunction with machine learning, we improve …

Autoimmune Polyglandular Syndrome Type 1: A Case Report And Brief Review., Ifeanyi Nwosu, Oreoluwa Oladiran, Chinyere Ogbonna-Nwosu, Anulika Anyata

Reading Hospital Internal Medicine Residency

Autoimmune polyglandular syndrome (APS) type 1 is a rare autoimmune disorder inherited in an autosomal recessive pattern due to loss of function of the AIRE gene and defective removal of self-reactive T-lymphocytes during the process of thymic T cell maturation. Its manifestation starts early in life with the cardinal clinical disorders being one of muco-cutaneous candidiasis, Addison's disease, and hypoparathyroidism. Recognizing the syndromic nature of one autoimmune disease will facilitate an active search for other conditions which would allow early detection, management, follow-up, and most importantly patient education and counselling to avoid potential complications. We present the case of a …

Leptin Produced By Obesity-Altered Adipose Stem Cells Promotes Metastasis But Not Tumorigenesis Of Triple-Negative Breast Cancer In Orthotopic Xenograft And Patient-Derived Xenograft Models, Rachel A. Sabol, Annie C. Bowles, Alex Côté, Rachel Wise, Benjamen O'Donnell, Margarite D. Matossian, Fokhrul M. Hossain, Hope E. Burks, Luis Del Valle, Lucio Miele, Bridgette M. Collins-Burow, Matthew E. Burow, Bruce A. Bunnell

School of Medicine Faculty Publications

BACKGROUND: Breast cancer is the second leading cause of cancer deaths in the USA. Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer with high rates of metastasis, tumor recurrence, and resistance to therapeutics. Obesity, defined by a high body mass index (BMI), is an established risk factor for breast cancer. Women with a high BMI have increased incidence and mortality of breast cancer; however, the mechanisms(s) by which obesity promotes tumor progression are not well understood. METHODS: In this study, obesity-altered adipose stem cells (obASCs) were used to evaluate obesity-mediated effects of TNBC. Both in vitro …

Gnrh Agonist Improves Hyperandrogenism In An Adolescent Girl With An Insulin Receptor Gene Mutation., Emily Paprocki, Romina Barral, Heidi Vanden Brink, Marla Lujan, Tania S. Burgert

Manuscripts, Articles, Book Chapters and Other Papers

Type A insulin resistance (IR) is caused by heterozygous mutations in the insulin receptor gene. It presents with mild acanthosis nigricans, severe IR, and hyperandrogenism in the absence of obesity or lipodystrophy. Treatment aims to improve insulin sensitivity and decrease androgens. An adolescent girl was evaluated for secondary amenorrhea and prominent hirsutism. She had a normal body mass index, and laboratory testing revealed an elevated LH to FSH ratio (LH 11.6 mIU/mL, FSH 4.2 mIU/mL), testosterone 96 ng/dL (reference range/dL), free testosterone 2.21 ng/dL (reference rangeA(pGly1032Asp)]. After standard treatment of hirsutism and hyperinsulinism failed, a trial of GnRH agonist therapy …

Viral Whole Genome Sequencing For Antiviral Resistance In A Child With Dock8 Deficiency And Recurrent Hsv-1, Sean Stout, A. L. Greninger, Rangaraj Selvarangan, A. F. Freeman, Brandon D. Newell, Erin Stahl, Dwight Yin

Posters

We present the case of a child with dedicator of cytokinesis 8 (DOCK8) deficiency and chronic, resistant HSV-1 mucocutaneous infections to illustrate the clinical utility of viral whole genome sequencing to detect active and latent HSV resistance mutations.

Differential Iron Regulatory Genetics In 2d & 3d Culture Of Breast Cancer Cells, Tyler Hanna, Suzy Torti Ph. D, Frank Torti M.D., Mph, Nicole Farra Ph. D.

Honors Scholar Theses

The iron regulatory axis has consistently been shown to be perturbed in cancer cell lines relative to non-cancerous cell lines. As cancer cells rapidly divide and grow, they require iron to fuel many intracellular processes, including DNA replication and protein synthesis. Three-dimensional cell culture is an increasingly popular method of culture that purportedly more accurately mimics the in vivo microenvironment of cancers over traditional two-dimensional culture. This project was prompted by previous lab results to investigate differential iron regulatory gene expression in 2D and 3D spheroid culture models. We replicated the findings that the gene hepcidin is induced in 3D …

Exploring The Potential Yield Of Prenatal Testing By Evaluating A Postnatal Population With Structural Abnormalities, Peyton Busby

Dissertations and Theses (Open Access)

After identification of one or more structural abnormalities in a fetus, pregnant women are offered a host of different testing options to identify a possible genetic cause for the structural abnormality(ies). When considering what type of test to undertake, there is limited information on the diagnostic yield of the varying testing options. Some women may miss an opportunity to gain the information they are seeking or make a less informed decision when they choose a testing option after identification of a structural abnormality due to this lack of information. This study aimed to identify the potential diagnostic yield of all …

Neuroblastoma In Adolescents And Children Older Than 10 Years: Unusual Clinicopathologic And Biologic Features, Laura Mccarthy, Katherine Chastain, Terrie Flatt, Eugenio Taboada, Robert E. Garola, John Herriges, Linda D. Cooley, Atif Ahmed

Posters

This poster describes four cases of neuroblastoma diagnosed since 2008 in children greater than 10 years and presents their clinical, histologic and biologic features, emphasizing unusual clinicopathologic characteristics and the role of DNA microarray analysis and Next Generation Sequencing in their management.

Ucp1 Expression-Associated Gene Signatures Of Human Epicardial Adipose Tissue., Kanta Chechi, Jinchu Vijay, Pierre Voisine, Patrick Mathieu, Yohan Bossé, Andre Tchernof, Elin Grundberg, Denis Richard

Manuscripts, Articles, Book Chapters and Other Papers

Multiple reports of uncoupling protein 1 (UCP1) expression have established its presence in human epicardial adipose tissue (eAT). Its functional relevance to eAT, however, remains largely unknown. In a recent study, we reported that adrenergic stimulation of eAT was associated with downregulation of secreted proteins involved in oxidative stress-related and immune-related pathways. Here, we explored the UCP1-associated features of human eAT using next-generation deep sequencing. Paired biopsies of eAT, mediastinal adipose tissue (mAT), and subcutaneous adipose tissue (sAT) obtained from cardiac surgery patients, with specific criteria of high and low expression of UCP1 in eAT, were subjected to RNA sequencing. …

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to engineer …

Prefrontal Corticotropin-Releasing Factor (Crf) Neurons Act Locally To Modulate Frontostriatal Cognition And Circuit Function., Sofiya Hupalo, Andrea J Martin, Rebecca K Green, David M Devilbiss, Craig W Berridge

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRF-dependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated …

Early Progression Of Krabbe Disease In Patients With Symptom Onset Between 0 And 5 Months., Maria L. Beltran-Quintero, Nicholas A. Bascou, Michele D. Poe, David A. Wenger, Carlos A. Saavedra-Matiz, Matthew J. Nichols, Maria L. Escolar

Department of Neurology Faculty Papers

BACKGROUND: Krabbe disease is a rare neurological disorder caused by a deficiency in the lysosomal enzyme, β-galactocerebrosidase, resulting in demyelination of the central and peripheral nervous systems. If left without treatment, Krabbe disease results in progressive neurodegeneration with reduced quality of life and early death. The purpose of this prospective study was to describe the natural progression of early onset Krabbe disease in a large cohort of patients.

METHODS: Patients with early onset Krabbe disease were prospectively evaluated between 1999 and 2018. Data sources included diagnostic testing, parent questionnaires, standardized multidisciplinary neurodevelopmental assessments, and neuroradiological and neurophysiological tests.

RESULTS: We …

Is Retinal Metabolic Dysfunction At The Center Of The Pathogenesis Of Age-Related Macular Degeneration?, Thierry Léveillard, Nancy J. Philp, Florian Sennlaub

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The retinal pigment epithelium (RPE) forms the outer blood⁻retina barrier and facilitates the transepithelial transport of glucose into the outer retina via GLUT1. Glucose is metabolized in photoreceptors via the tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS) but also by aerobic glycolysis to generate glycerol for the synthesis of phospholipids for the renewal of their outer segments. Aerobic glycolysis in the photoreceptors also leads to a high rate of production of lactate which is transported out of the subretinal space to the choroidal circulation by the RPE. Lactate taken up by the RPE is converted to pyruvate and metabolized …

Identification Of Novel Regulatory Genes In Apap Induced Hepatocyte Toxicity By A Genome-Wide Crispr-Cas9 Screen., Katherine Shortt, Daniel P. Heruth, Nini Zhang, Weibin Wu, Shipra Singh, Ding-You Li, Li Qin Zhang, Gerald J. Wyckoff, Lei S Qi, Craig A. Friesen, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15 mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, …

Clinical Genome Sequencing In An Unbiased Pediatric Cohort., Isabelle Thiffault, Emily G. Farrow, Lee Zellmer, Courtney D. Berrios, Neil Miller, Margaret Gibson, Raymond Caylor, Janda L. Jenkins, Deb Faller, Sarah E. Soden, Carol J. Saunders

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: We report for the first time, the use of clinical genome sequencing (GS) in an unbiased pediatric cohort. We describe the clinical validation, patient metrics, ordering patterns, results, reimbursement, and physician retrieval of results for the first consecutive 80 cases.

METHODS: Clinical GS was performed for both inpatients and outpatients undergoing etiologic evaluations. Results were reported in the electronic medical record. Evidence of report retrieval by clinicians and whether interpretation was concordant with laboratory report was obtained through retrospective chart review.

RESULTS: Twenty definitive diagnoses were made in 19 patients (24%; n = 80). Except for two partial gene …

Coordinating An Oncology Precision Medicine Clinic Within An Integrated Health System: Lessons Learned In Year One, Michael A. Thompson, Jennifer J. Godden, Deborah Wham, Antony Ruggeri, Michael P. Mullane, Amanda Wilson, Shamsuddin Virani, Scott M. Weissman, Brenda Ramczyk, Pamela Vanderwall, James L. Weese

Journal of Patient-Centered Research and Reviews

Precision medicine is a term describing strategies to promote health and prevent and treat disease based on an individual’s genetic, molecular, and lifestyle characteristics. Oncology precision medicine (OPM) is a cancer treatment approach targeting cancer-specific genetic and molecular alterations. Implementation of an OPM clinical program optimally involves the support and collaboration of multiple departments, including administration, medical oncology, pathology, interventional radiology, genetics, research, and informatics. In this review, we briefly introduce the published evidence regarding OPM’s potential effect on patient outcomes and discuss what we have learned over the first year of operating an OPM program within an integrated health …

The Copy Number Variation Landscape Of Congenital Anomalies Of The Kidney And Urinary Tract., Miguel Verbitsky, Rik Westland, Alejandra Perez, Krzysztof Kiryluk, Qingxue Liu, Priya Krithivasan, Adele Mitrotti, David A. Fasel, Ekaterina Batourina, Matthew G. Sampson, Monica Bodria, Max Werth, Charlly Kao, Jeremiah Martino, Valentina P. Capone, Asaf Vivante, Shirlee Shril, Byum Hee Kil, Maddalena Marasà, Jun Y. Zhang, Young-Ji Na, Tze Y. Lim, Dina Ahram, Patricia L. Weng, Erin L. Heinzen, Alba Carrea, Giorgio Piaggio, Loreto Gesualdo, Valeria Manca, Giuseppe Masnata, Maddalena Gigante, Daniele Cusi, Claudia Izzi, Francesco Scolari, Joanna A E Van Wijk, Marijan Saraga, Domenico Santoro, Giovanni Conti, Pasquale Zamboli, Hope White, Dorota Drozdz, Katarzyna Zachwieja, Monika Miklaszewska, Marcin Tkaczyk, Daria Tomczyk, Anna Krakowska, Przemyslaw Sikora, Tomasz Jarmoliński, Maria K. Borszewska-Kornacka, Robert Pawluch, Maria Szczepanska, Piotr Adamczyk, Malgorzata Mizerska-Wasiak, Grazyna Krzemien, Agnieszka Szmigielska, Marcin Zaniew, Mark G. Dobson, John M. Darlow, Prem Puri, David E. Barton, Susan L. Furth, Bradley A. Warady, Zoran Gucev, Vladimir J. Lozanovski, Velibor Tasic, Isabella Pisani, Landino Allegri, Lida M. Rodas, Josep M. Campistol, Cécile Jeanpierre, Shumyle Alam, Pasquale Casale, Craig S. Wong, Fangming Lin, Débora M. Miranda, Eduardo A. Oliveira, Ana Cristina Simões-E-Silva, Jonathan M. Barasch, Brynn Levy, Nan Wu, Friedhelm Hildebrandt, Gian Marco Ghiggeri, Anna Latos-Bielenska, Anna Materna-Kiryluk, Feng Zhang, Hakon Hakonarson, Virginia E. Papaioannou, Cathy L. Mendelsohn, Ali G. Gharavi, Simone Sanna-Cherchi

Manuscripts, Articles, Book Chapters and Other Papers

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; and vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, …