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

Neighborhood Environment And Poor Maternal Glycemic Control-Associated Complications Of Gestational Diabetes Mellitus, Leela V. Thomas, Claudine T. Jurkovitz, Zugui Zhang, Mitchell R. Fawcett, M. James Lenhard

Department of Medicine Faculty Papers

INTRODUCTION: Risk of complications due to gestational diabetes mellitus is increasing in the U.S., particularly among individuals from racial minorities. Research has focused largely on clinical interventions to prevent complications, rarely on individuals' residential environments. This retrospective cohort study aims to examine the association between individuals' neighborhoods and complications of gestational diabetes mellitus.

METHODS: Demographic and clinical data were extracted from electronic health records and linked to American Community Survey data from the U.S. Census Bureau for 2,047 individuals who had 2,164 deliveries in 2014-2018. Data were analyzed in 2021-2022 using Wilcoxon rank sum test and chi-square test for bivariate …

A Phenotypically Robust Model Of Spinal And Bulbar Muscular Atrophy In Drosophila, Kristin Richardson, Medha Sengupta, Alyson Sujkowski, Kozeta Libohova, Autumn C. Harris, Robert Wessells, Diane E. Merry, Sokol V. Todi

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is an X-linked disorder that affects males who inherit the androgen receptor (AR) gene with an abnormal CAG triplet repeat expansion. The resulting protein contains an elongated polyglutamine (polyQ) tract and causes motor neuron degeneration in an androgen-dependent manner. The precise molecular sequelae of SBMA are unclear. To assist with its investigation and the identification of therapeutic options, we report here a new model of SBMA in Drosophila melanogaster. We generated transgenic flies that express the full-length, human AR with a wild-type or pathogenic polyQ repeat. Each transgene is inserted into the same safe …

Human Parechovirus Central Nervous System Infection In A Young Infant Cohort, Aspasia Katragkou, Avni Sheth, Christina Gagliardo, Jessica Aquino, Niva Shah, Eberechi Nwaobasi-Iwuh, Christina Melchionne, Paige Black, Stephanie Chiu, Cecilia Di Pentima

Department of Pediatrics Faculty Papers

In 2022, a surge in cases of pediatric human parechovirus (HPeV) central nervous system infections in young infants was seen at our institution. Despite the dramatic increase in the number of cases seen that year, the clinical features of the illness were similar to prior years. The recent pediatric HPeV surge highlights the need to evaluate treatment options and standardize follow-up to better understand the long-term prognosis of infants with HPeV infection.

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 …

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 …

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 …