Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons^™

Genome Editing For Cystic Fibrosis, Guoshun Wang

School of Medicine Faculty Publications

Cystic fibrosis (CF) is a monogenic recessive genetic disorder caused by mutations in the CF Transmembrane-conductance Regulator gene (CFTR). Remarkable progress in basic research has led to the discovery of highly effective CFTR modulators. Now ~90% of CF patients are treatable. However, these modulator therapies are not curative and do not cover the full spectrum of CFTR mutations. Thus, there is a continued need to develop a complete and durable therapy that can treat all CF patients once and for all. As CF is a genetic disease, the ultimate therapy would be in-situ repair of the genetic lesions in the …

Clinical Spectrum And Genetic Causes Of Mitochondrial Hepatopathy Phenotype In Children, James E Squires, Alexander G Miethke, C Alexander Valencia, Kieran Hawthorne, Lisa Henn, Johan L K Van Hove, Robert H Squires, Kevin Bove, Simon Horslen, Rohit Kohli, Jean P Molleston, Rene Romero, Estella M Alonso, Jorge A Bezerra, Stephen L Guthery, Evelyn Hsu, Saul J Karpen, Kathleen M Loomes, Vicky L Ng, Philip Rosenthal, Krupa Mysore, Kasper S Wang, Marisa W Friederich, John C Magee, Ronald J Sokol, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND: Alterations in both mitochondrial DNA (mtDNA) and nuclear DNA genes affect mitochondria function, causing a range of liver-based conditions termed mitochondrial hepatopathies (MH), which are subcategorized as mtDNA depletion, RNA translation, mtDNA deletion, and enzymatic disorders. We aim to enhance the understanding of pathogenesis and natural history of MH.

METHODS: We analyzed data from patients with MH phenotypes to identify genetic causes, characterize the spectrum of clinical presentation, and determine outcomes.

RESULTS: Three enrollment phenotypes, that is, acute liver failure (ALF, n = 37), chronic liver disease (Chronic, n = 40), and post-liver transplant (n = 9), were analyzed. …

Implementing A Hearing Screening Readiness Assessment Tool For Preterm And Term Neonates In The Newborn Intensive Care Unit: A Pilot Project, Mckenzie Blatt, Adrienne Johnson, Jennifer L. Hamilton, Carly Alston, Belinda Chan

Journal of Early Hearing Detection and Intervention

Newborn intensive care unit (NICU) patients are at risk for hearing loss. Early detection mitigates consequences of speech and language delay. The Joint Committee on Infant Hearing (JCIH) recommends hearing screening (HS) on all infants by 1 month of age. Often hearing screening is performed around the time of NICU discharge, often beyond JCIH recommendations. Automated auditory brainstem response (AABR) screening can be performed once an infant reaches 32 to 34 weeks corrected gestational age (GA). Our project aimed to reduce HS delay among NICU infants. We created and implemented a HS assessment tool defining gestational age and medical stability …

Mechanisms Of Mutated Myosin Vb Mediated Cholestasis In Microvillus Inclusion Disease, Melissa S. Holzapfel

Theses & Dissertations

Microvillus inclusion disease (MVID) is a constitutive intestinal epithelial disease which causes definitive intestinal failure and cholestatic liver disease primarily caused by mutations in the Myosin Vb gene. Genotype-clinical phenotype associations suggest that the progression of liver disease can be predicted through a correlation between myosin Vb residual function and variable retention of bile salt transport machinery in intestinal enterocytes and liver hepatocytes. We proposed that aberrant distribution of bile salt transport proteins disrupts enterohepatic regulation of bile acids and contributes to the progression of cholestatic liver disease. To investigate the genotype-phenotype correlation, samples from MVID patients were evaluated for …

The Effects Of Prenatal Buprenorphine Exposure On The Neurobehavioral Development Of The Child, Zaineb Zubair, Maryam Zubair, Juan Alonso, Abdullah Zubair

Rowan-Virtua Research Day

Background: Current guidelines for pregnant women with substance use disorder advise prenatal maintenance of opioid agonist therapy with either buprenorphine or methadone. Despite this rise in prenatal opioid agonist therapy, little is known about the effect of prenatal buprenorphine on the neurobehavioral development of the child. This poses the question: does buprenorphine have a long-lasting effect on the central and peripheral nervous system development and behavior of children who were exposed prenatally?

Methods: A comprehensive literature review identified articles relating to prenatal buprenorphine and neurobehavioral outcomes. Article searches were conducted on PubMed and Dynamed. Publications from 2002 through November 2021 …

Inflammatory Marker Levels Among Patients Diagnosed With Autism Spectrum Disorder And Congenital Heart Defects, Patrick Pearce, Venkateswar Venkataraman, Andrea Iannuzzelli, Jennifer Lecomte

Rowan-Virtua Research Day

Autism Spectrum Disorder (ASD) and congenital heart defects (CHD) are conditions that both confer an immense increase in standard of care, and utilization of medical resources addressing comorbidities. One shared symptom that has been consistently cited is inflammation. This review sought to explore the levels of Tumor Necrosis Factor-�� (TNF-��) and Interleukin-6 (IL-6) between patients diagnosed as having either ASD or CHD. By compiling published data containing the mean values of these two inflammatory markers within these populations, it was shown that while both have significantly elevated levels compared to a phenotypically normal demographic, there is no significant difference between …

Is There An Association Between Preeclampsia/Eclampsia And Congenital Heart Disease Among The Neurodivergent Population?, Jasmine Emanuel, Venkateswar Venkataraman, Jennifer Lecomte, Andrea Iannuzzelli

Rowan-Virtua Research Day

Preeclampsia and eclampsia are very common gestational conditions among pregnant individuals worldwide. These individuals are diagnosed with high blood pressure (after 20 weeks of gestation), proteinuria/end-stage organ disease, and may include seizures. These conditions can put the mother and fetus at risk. A review of literature has shown that there is an association between cardiovascular defects among the neurodivergent population, where these individuals have a higher risk of developing atrial septal defects and ventricular septal defects. The Rowan-Virtua Integrated Special Needs (RISN) Center patient population will be used to investigate whether preeclampsia/eclampsia in mothers is indicative of higher congenital heart …

Case Report: Uterine Torsion – A Rare Cause Of Right Lower Quadrant Pain, David Ho, James Jung Lee, James Espinosa

Rowan-Virtua Research Day

Uterine torsions are very rare. In an article by Matsumoto et al published in 2021, only 25 cases have been documented on PubMed in non-gravid females in the past 20 years. Uterine torsion is defined as rotation of the uterus greater than 45 degrees in the long axis. Rotation can occur anywhere between 45 degrees to 180 degrees. The torsion can be due to a congenital anomaly or an obstetrics emergency such as with an ovarian torsion. Uterine torsions presenting as an obstetrics emergency carries the potential for irreversible ischemic damage to the uterus, and just as in ovarian torsion, …

Association Of Prematurity And Urogenital Comorbidities With Postoperative Outcomes Of Ureteroneocystostomy For Vesicoureteral Reflux, Raeann Dalton, Young Son, Edward Wu, Leah Anderton, Matthew Eximond, Lance Earnshaw, Katelyn Klimowich, Gregory Dean

Rowan-Virtua Research Day

Background: It is estimated that 20-30% of congenital anomalies involve the kidney and ureter, and these rates are even higher in infants with low birth weights. Vesicoureteral reflux (VUR) occurs when there is a backflow of urine from the bladder to the kidney. Depending on severity, this condition may require surgical correction with ureteroneocystostomy (UNC). The impact of premature birth and presence of urogenital comorbidities on outcomes of UNC is not known. The objective of this study is to determine the relationship between premature birth and urogenital comorbidities with operative outcomes of UNC for VUR.

Methods: The 2020 American College …

Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone

Rowan-Virtua Research Day

Canavan disease (CD) is an inherited leukodystrophy caused by inactivating mutations to the glial enzyme aspartoacylase (ASPA). ASPA catabolizes neuronal N-acetylaspartate (NAA) into free acetate and aspartate and loss of this function results in the chronic elevation of non-catabolized NAA and the failure of developmental myelination. Elevated NAA is thought to cause damage to myelin and myelin-producing cells (oligodendrocytes, but the viability of neurons in CD is relatively unexplored. We compare here the progressive degeneration of neurons in two regions of the CD mouse brain, the thalamus and the cortex, distinguished by differing degrees of vacuolation, and show that the …

Congenital L-Transposition Of The Great Arteries In A 12-Year-Old: A Case Report, Muhammad Noman

Rowan-Virtua Research Day

Levo-transposition of the great arteries, L-TGA, also known as congenitally corrected transposition, cc-TGA is a rare anomaly and accounts for less than 1% of all congenital heart diseases. It is characterized by both atrioventricular and ventriculoarterial discordance . It is considered a congenitally corrected transposition because the circulation is from right atrium to left ventricle leading to the pulmonary vasculature. The lungs then pump blood into the left atrium to the right ventricle and eventually to the systemic circulation via the aorta.

Development Of Schizophrenia In A Genetically Predisposed Individual Following Covid-19, Sung Kang, Jonathan Yuh, Timothy Wong

Rowan-Virtua Research Day

We present a patient who is a 56-year-old female with a psychiatric history of anxiety disorder and a medical history of hypercholesterolemia and hyperthyroidism, who was admitted to the hospital after a witnessed seizure at an inpatient psychiatric facility. This patient’s family history is significant for her mother experiencing unspecified psychotic disorder that required psychiatric hospitalization. Our patient was first admitted to the psychiatric hospital after exhibiting worsening paranoid delusions and hallucinations that began several months prior. The patient had reportedly begun locking herself in the restroom and screaming “get out, they’re spying on me”, referring to her next-door neighbors …

Contemporary Homozygous Familial Hypercholesterolemia In The United States: Insights From The Cascade Fh Registry, Marina Cuchel, Paul C. Lee, Lisa C. Hudgins, P. Barton Duell, Zahid Ahmad, Seth J. Baum, Macrae F. Linton, Sarah D. De Ferranti, Christie M. Ballantyne, John A. Larry, Linda C. Hemphill, Iris Kindt, Samuel S. Gidding, Seth S. Martin, Patrick M. Moriarty, Paul P. Thompson, James A. Underberg, John R. Guyton, Rolf L. Andersen, David J. Whellan, Irwin Benuck, John P. Kane, Kelly Myers, William Howard, David Staszak, Allison Jamison, Mary C. Card, Mafalda Bourbon, Joana R. Chora, Daniel J. Rader, Joshua W. Knowles, Katherine Wilemon, Mary P. Mcgowan

Division of Cardiology Faculty Papers

Background

Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment‐resistant disorder characterized by early‐onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain.

Methods and Results

Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the …

Determining The Effects Of Maternal Adiposity On Preterm Neonatal Microbiome And Short Chain Fatty Acid Profiles, Dalton James, William A. Clark Phd, Kristy L. Thomas

Undergraduate Honors Theses

The gut microbiota and its metabolites have vast impacts on the human digestive system, immune system, and health outcomes. Short chain volatile fatty acids (SCVFAs) present in feces can be representative of the interactions of the microbiota present in the gut. Low microbiota diversity in the human gut is highly associated with obesity and adverse health outcomes. Furthermore, the maternal microbiome has a direct impact on neonatal microbiota through various pathways such as environment, skin flora, breast milk composition, and vaginal secretions. This study is aimed to further understand the associations between various factors (maternal adiposity, gestational time, length of …

Impacts Of Dietary Restriction On A Drosophila Model Of Werner Syndrome, Eileen Sember

College of Arts & Sciences Senior Theses

Werner syndrome (WS) is an autosomal recessive disorder that results in premature aging and occurs in 1 in 1,000,0000 to 1 in 10,000,000 people. In humans, WS is the result of mutations that render the WRN gene, that contains a helicase and an exonuclease domain, non-functional. Currently, there is no cure for WS in humans, making dietary and lifestyle interventions attractive for increasing the quality and longevity of lives. Diet restriction (DR) has been shown to extend the lifespan of several model organisms, including Drosophila melanogaster, making it a strong candidate for WS treatment. In this thesis, mutant flies …

Perceived Utility Of Genetic Carrier Screening In A Diverse Patient Population, Jack A. Colleran

Dissertations and Theses (Open Access)

Carrier screening assesses whether an individual may carry variants in select genes associated with autosomal recessive and X-linked inheritance. Recent American College of Medical Geneticists (ACMG) guidelines call for utilization of expanded screening that analyzes carrier status for up to hundreds of conditions. In these guidelines, clinical utility is based on alterations to reproductive decision-making. However, clinical utility study cohorts cited by these guidelines were largely white, highly educated, of high income, and were often receiving preconception counseling. There is a lack of research on the perspectives of patients from diverse backgrounds, whose perceptions may be more reflective of those …

Rare Presentation Of Primary Malignant Peripheral Nerve Sheath Tumor Of The Femur In Neurofibromatosis-1, Akshaj Pole, Danielle Ford, Elizabeth Pollard

North Texas GME Research Forum 2023

Malignant peripheral nerve sheath tumors (MPNSTs) are rare sarcomas, most commonly seen in patients with Neurofibromatosis type 1 (NF1), that are characterized as aggressive with high rate of local recurrence. Among NF1 patients, the risk of developing MNPSTs is approximately 8-13% over a lifetime. Primary MPNST is exceedingly rare, of which the vast majority are concentrated in the head and neck region. Here, we present a case of a 40-year-old male with NF1 who presented with a giant MPNST that originated in the right proximal femur. The mass was treated with complete surgical resection with right hip disarticulation. In a …

The Domino Effect: Spontaneous Abortions As A Sequela Of Eisenmenger Syndrome, Riddhiben Patel, Anas Hamadeh, Laura Montoya, Senthil Thambidorai

North Texas GME Research Forum 2023

Background: Eisenmenger's syndrome (ES) is a congenital cardiac abnormality in which a significant chronic left-to-right shunt results in pulmonary arterial hypertension and a reversal of the shunting direction. A woman with ES should ideally avoid conception given the increased risk of unexpected fetal demise and maternal mortality. Case: We present a case of a 35-year-old female patient G3, P0, at 9 weeks gestation with reported PMHx of erythrocytosis and spontaneous abortions who presented to the hospital with complaints of vaginal bleeding and worsening SOB. She was noted to have a Hct of 70 and a Hb of 23.8, with SaO2 …

A Rare Case Of Persistent Left Superior Vena Cava Discovered During An Intracardiac Echocardiography Procedure, Riddhi H. Patel, Bilal Ayub

North Texas GME Research Forum 2023

Background: Isolated persistent left superior vena cava (PLSVC), also known as persistent left superior vena cava (SVC) with absent right SVC, affects 0.09-0.13% of the population. Right SVC is present in the majority of people with left SVC. Rarely, the right SVC may be missing. Here, we discuss a rare case of PLSVC found incidentally in a patient with paroxysmal atrial fibrillation (PAF).

Case: A 63-year-old female patient with a history of Paroxysmal Atrial flutter (AFL) and atrial fibrillation (AF) on apixaban, HTN, and HLD was brought to the electrophysiology lab for electrophysiology study (EPS) and AF/AFL ablation due to …

A Rare Case Of Von Gierke Causing Severe Aortic Stenosis, Srujana Dasari, Akhil R. Gade, Nethuja Salagundla, Chandralekha Ashangari, Rashonda Carlisle

North Texas GME Research Forum 2023

Von Gierke disease is an inherited Glycogen Storage disease - type 1 resulting from deficiencies in the specific enzymes glucose 6 phosphatase(1a), and/or glucose 6 phosphate translocase(1b) glycogen metabolism pathway. Von Gierke disease is commonly seen in the pediatric population and is known for his hepatic and renal manifestations. Here we discuss a rare case of Von Gierke’s disease causing some rare cardiac manifestations. 41yo M with PMHx significant for Von Gierke type 1a, HFrEF complicated by VT s/p ICD, HTN who presented for complaints of continued SOB with new muscle soreness. On arrival, lactic acid was elevated at 5.2, …