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

A Cryptic Microdeletion Del(12)(P11.21p11.23) Within An Unbalanced Translocation T(7;12)(Q21.13;Q23.1) Implicates New Candidate Loci For Intellectual Disability And Kallmann Syndrome, Afif Ben-Mahmoud, Shotaro Kishikawa, Vijay Gupta, Natalia T. Leach, Yiping Shen, Oana Moldovan, Himanshu Goel, Bruce Hopper, Kara Ranguin, Nicolas Gruchy, Saskia M. Maas, Yves Lacassie, Soo Hyun Kim, Woo Yang Kim, Bradley J. Quade, Cynthia C. Morton, Cheol Hee Kim, Lawrence C. Layman, Hyung Goo Kim

School of Medicine Faculty Publications

In a patient diagnosed with both Kallmann syndrome (KS) and intellectual disability (ID), who carried an apparently balanced translocation t(7;12)(q22;q24)dn, array comparative genomic hybridization (aCGH) disclosed a cryptic heterozygous 4.7 Mb deletion del(12)(p11.21p11.23), unrelated to the translocation breakpoint. This novel discovery prompted us to consider the possibility that the combination of KS and neurological disorder in this patient could be attributed to gene(s) within this specific deletion at 12p11.21-12p11.23, rather than disrupted or dysregulated genes at the translocation breakpoints. To further support this hypothesis, we expanded our study by screening five candidate genes at both breakpoints of the chromosomal translocation …

Incorporating Poi As A Therapeutic Modality For Preschool Aged Children In The Care Clinic, Danielle Zirkle

Department of Occupational Therapy Entry-Level Capstone Projects

No abstract provided.

Mid-Life Leukocyte Telomere Length And Dementia Risk: An Observational And Mendelian Randomization Study Of 435,046 Uk Biobank Participants, Rui Liu, Luke C. Pilling, David Melzer, Lihong Wang, Kevin J. Manning, David C. Steffens, Jack Bowden, Richard H. Fortinsky, George A. Kuchel, Taeho G. Rhee, Breno S. Diniz, Chia-Ling Kuo

Health Science Faculty Publications

Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data ( …

The Effect Of Genetic Taste Status On Swallowing: A Literature Review, Theresa S. Lee, Angela M. Dietsch, Rana H. Damra, Rachel W. Mulheren

Department of Special Education and Communication Disorders: Faculty Publications

Purpose

Swallowing and taste share innervation pathways and are crucial to nutritive intake. Individuals vary in their perception of taste due to factors such as genetics; however, it is unclear to what extent genetic taste status influences swallowing physiology and function. The purpose of this review article is to provide background on genetic taste status, review the evidence on the association between genetic taste status and swallowing, and discuss research and clinical implications.

Method

A comprehensive literature review was conducted using search terms related to swallowing and genetic taste status. Studies were included if they investigated the main effect of …

Lifelong Fitness In Ambulatory Children And Adolescents With Cerebral Palsy I: Key Ingredients For Bone And Muscle Health, Noelle G. Moreau, Kathleen M. Friel, Robyn K. Fuchs, Sudarshan Dayanidhi, Theresa Sukal-Moulton, Marybeth Grant-Beuttler, Mark D. Peterson, Richard D. Stevenson, Susan V. Duff

Physical Therapy Faculty Articles and Research

Physical activity of a sufficient amount and intensity is essential to health and the prevention of a sedentary lifestyle in all children as they transition into adolescence and adulthood. While fostering a fit lifestyle in all children can be challenging, it may be even more so for those with cerebral palsy (CP). Evidence suggests that bone and muscle health can improve with targeted exercise programs for children with CP. Yet, it is not clear how musculoskeletal improvements are sustained into adulthood. In this perspective, we introduce key ingredients and guidelines to promote bone and muscle health in ambulatory children with …

Evaluation Of The Orally Bioavailable 4-Phenylbutyrate-Tethered Trichostatin A Analogue Ar42 In Models Of Spinal Muscular Atrophy, Casey J. Lumpkin, Ashlee W. Harris, Andrew J. Connell, Ryan W. Kirk, Joshua A. Whiting, Luciano Saieva, Livio Pellizzoni, Arthur H.M. Burghes, Matthew E.R. Butchbach

Department of Pediatrics Faculty Papers

Proximal spinal muscular atrophy (SMA) is a leading genetic cause for infant death in the world and results from the selective loss of motor neurons in the spinal cord. SMA is a consequence of low levels of SMN protein and small molecules that can increase SMN expression are of considerable interest as potential therapeutics. Previous studies have shown that both 4-phenylbutyrate (4PBA) and trichostatin A (TSA) increase SMN expression in dermal fibroblasts derived from SMA patients. AR42 is a 4PBA-tethered TSA derivative that is a very potent histone deacetylase inhibitor. SMA patient fibroblasts were treated with either AR42, AR19 (a …

Lifelong Fitness In Ambulatory Children And Adolescents With Cerebral Palsy Ii: Influencing The Trajectory, Susan V. Duff, Justine D. Kimbel, Marybeth Grant-Beuttler, Theresa Sukal-Moulton, Noelle G. Moreau, Kathleen M. Friel

Physical Therapy Faculty Articles and Research

Physical activity of at least moderate intensity in all children contributes to higher levels of physical and psychological health. While essential, children with cerebral palsy (CP) often lack the physical capacity, resources, and knowledge to engage in physical activity at a sufficient intensity to optimize health and well-being. Low levels of physical activity place them at risk for declining fitness and health, contributing to a sedentary lifestyle. From this perspective, we describe a framework to foster a lifelong trajectory of fitness in ambulatory children with CP (GMFCS I–III) as they progress into adolescence and adulthood, implemented in conjunction with a …

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 …

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 …

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 …

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-𝞪 (TNF-𝞪) 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 …

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 …

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, …

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.

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 …

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 …

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

College of Arts & Sciences Senior Honors 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 …