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

Outcomes Of Allogeneic Hematopoietic Stem Cell Transplantation For Gata2 And Dock8 Immunodeficiencies: Demographics And Transplantation Variables, Kristen M. Cole, Dnp, Msn, Rn, Bmtcn, Ocn

Doctor of Nursing Practice Projects

Background/Purpose: GATA2 and Dedicator-of-Cytokinesis-8 (DOCK8) deficiencies are two recently described genetic immunodeficiency diseases for which allogeneic hematopoietic stem cell transplant (HSCT) represents the only definitive therapy. The patient characteristics and HSCT variables that relate to the outcomes in these two diseases following HSCT remain unclear. Therefore, we described these variables in these two patient populations and explored their relationships with HSCT outcomes.

Methods: Data were obtained from retrospective chart reviews of all patients with GATA2 deficiency and DOCK8 deficiency who underwent HSCT on clinical research protocols at the National Cancer Institute. The outcomes included overall and disease-free survival status, graftversus-host …

Aberrant Brain Functional Connectivity In Newborns With Congenital Heart Disease Before Cardiac Surgery, Josepheen De Asis-Cruz, Mary T. Donofrio, Gilbert Vezina, Catherine Limperopoulos

Pediatrics Faculty Publications

Newborns with congenital heart disease (CHD) requiring open heart surgery are at increased risk for neurodevelopmental disabilities. Recent quantitative MRI studies have reported disrupted growth, microstructure, and metabolism in fetuses and newborns with complex CHD. To date, no study has examined whether functional brain connectivity is altered in this high-risk population after birth, before surgery. Our objective was to compare whole-brain functional connectivity of resting state networks in healthy, term newborns (n = 82) and in term neonates with CHD before surgery (n = 30) using graph theory and network-based statistics. We report for the first time intact global network …

Cost-Effectiveness Analysis Of Neonatal Screening Of Critical Congenital Heart Defects In China., Ruoyan Gai Tobe, Gerard R Martin, Fuhai Li, Akinori Moriichi, Bin Wu, Rintaro Mori

Pediatrics Faculty Publications

Background: Pulse oximetry screening is a highly accurate tool for the early detection of critical congenital heart disease (CCHD) in newborn infants. As the technique is simple, noninvasive, and inexpensive, it has potentially significant benefits for developing countries. The aim of this study is to provide information for future clinical and health policy decisions by assessing the costeffectiveness of CCHD screening in China.

Methods and Findings: We developed a cohort model to evaluate the cost-effectiveness of screening all Chinese newborns annually using 3 possible screening options compared to no intervention: pulse oximetry alone, clinical assessment alone, and pulse oximetry as …

The World Database For Pediatric And Congenital Heart Surgery: The Dawn Of A New Era Of Global Communication And Quality Improvement In Congenital Heart Disease., James D St Louis, Hiromi Kurosawa, Richard A Jonas, Nestor Sandoval, Jorge Cervantes, Christo I Tchervenkov, Jeffery P Jacobs, Kisaburo Sakamoto, Giovanni Stellin, James K Kirklin

Surgery Faculty Publications

No abstract provided.

Validating Candidate Congenital Heart Disease Genes In Drosophila., Jun-Yi Zhu, Yulong Fu, Adam Richman, Zhe Han

Pediatrics Faculty Publications

Genomic sequencing efforts can implicate large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system to validate candidate gene association with pathology is therefore useful. We present such a system employing Drosophila to validate candidate congenital heart disease (CHD) genes. The protocols exploit comprehensive libraries of UAS-GeneX-RNAi fly strains that when crossed into a 4×Hand-Gal4 genetic background afford highly efficient cardiac-specific knockdown of endogenous fly orthologs of human genes. A panel of quantitative assays evaluates phenotypic severity across multiple cardiac parameters. These include developmental lethality, larva and adult heart morphology, …

High Throughput In Vivo Functional Validation Of Candidate Congenital Heart Disease Genes In Drosophila., Jun-Yi Zhu, Yulong Fu, Margaret Nettleton, Adam Richman, Zhe Han

Pediatrics Faculty Publications

Genomic sequencing has implicated large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system is needed to validate gene associations with pathology. We developed a Drosophila-based functional system to screen candidate disease genes identified from Congenital Heart Disease (CHD) patients. 134 genes were tested in the Drosophila heart using RNAi-based gene silencing. Quantitative analyses of multiple cardiac phenotypes demonstrated essential structural, functional, and developmental roles for more than 70 genes, including a subgroup encoding histone H3K4 modifying proteins. We also demonstrated the use of Drosophila to evaluate cardiac phenotypes resulting …

Abnormal Glycosylation In Joubert Syndrome Type 10., Megan S Kane, Mariska Davids, Michelle R Bond, Christopher J Adams, Megan E Grout, Ian G Phelps, Gilbert Vezina, +Several Additional Authors

Neurology Faculty Publications

BACKGROUND: The discovery of disease pathogenesis requires systematic agnostic screening of multiple homeostatic processes that may become deregulated. We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10). He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.

METHODS: We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband. Analyses of cilia formation and lectin staining were performed by immunofluorescence. Measurement of cellular nucleotide sugar levels was performed with high-performance anion-exchange chromatography with pulsed amperometric …

Native T1 Values Identify Myocardial Changes And Stratify Disease Severity In Patients With Duchenne Muscular Dystrophy., Laura J. Olivieri, Peter Kellman, Robert J. Mccarter, Russell R. Cross, Michael S. Hansen, Christopher F. Spurney

Pediatrics Faculty Publications

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked, inherited disorder causing dilated cardiomyopathy with variable onset and progression. Currently we lack objective markers of the effect of therapies targeted towards preventing progression of subclinical cardiac disease. Thus, our aim was to compare the ability of native T1 and extracellular volume (ECV) measurements to differentiate risk of myocardial disease in DMD and controls.

METHODS: Twenty boys with DMD and 16 age/gender-matched controls without history predisposing to cardiac fibrosis, but with a clinical indication for cardiovascular magnetic resonance (CMR) evaluation, underwent CMR with contrast. Data points collected include left ventricular ejection fraction …

The Clinical, Biochemical And Genetic Features Associated With Rmnd1-Related Mitochondrial Disease., Yi Shiau Ng, Charlotte L Alston, Daria Diodato, Andrew A Morris, Nicole Ulrick, Stanislav Kmoch, +Several Additional Authors

Neurology Faculty Publications

BACKGROUND: Mutations in the RMND1 (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects.

METHODS: We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with RMND1 mutations. In addition, we reviewed all the previously published cases to determine the genotype-phenotype correlates and performed survival analysis to identify prognostic factors.

RESULTS: We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants: c.533C>A, p.(Thr178Lys); c.565C>T, p.(Gln189*); c.631G>A, p.(Val211Met); c.1303C>T, …

High Incidence Of Fracture Events In Patients With Long-Gap Esophageal Atresia (Lgea): A Retrospective Review Prompting Implementation Of Standardized Protocol., Sigrid Bairdain, Brenda Dodson, David Zurakowski, Lawrence Rhein, Brian D Snyder, Melissa Putman, Russell W Jennings

Surgery Faculty Publications

PURPOSE: To identify factors associated with an increased risk of fractures in Long-Gap Esophageal Atresia (LGEA) patients. Following implementation of a risk-stratified program, we hypothesized a reduction in fracture incidence within this potentially high-risk population.

METHODS: A retrospective review of LGEA-patients admitted between 2005 and 2014 was conducted. Symptomatic fractures with radiographic confirmation were defined as events. Univariate and multivariable analysis evaluated factors including admission weight-for-age z-score, primary versus secondary Foker process (FP), weight at Foker Stage I, days and episodes of paralysis, number of parenteral nutrition (PN) days, cumulative dose of loop diuretics adjusted for body weight and days …

Skinning The Surface Of Bone Abnormalities In Trichothiodystrophy, Rina Allawh, Michael Xiong, Deborah Tamura, John J. Digiovanna, Michael T. Collins, Kenneth H. Kraemer, Suvimol Hill

GW Research Days 2013

Objective(s): The purpose of the study conducted is to characterize the qualitative and quantitative features of the bone abnormalities present in patients diagnosed with Trichothiodystrophy (TTD), a DNA repair and transcription disorder. An additional goal of the study is to identify TTD patients at risk for rapidly progressive bone abnormalities in order to improve diagnosis and treatment for TTD patients.

Study Design: A retrospective study conducted at the National Institutes of Health (NIH) examining the bone abnormalities present in a study population comprised of 32 patients between the ages of 1 and 29 years of age diagnosed with TTD. Radiographic …