Medical Genetics Commons^™

Distinct Neuropsychological Profile And Associated Neurochemical Changes In Individuals With Mitochondrial Encephalomyopathy, Lactic Acidosis, And Stroke-Like Episodes (Melas), Emily B. Leaffer

All Dissertations, Theses, and Capstone Projects

Background: Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) is a maternally inherited progressive multisystemic disorder. Occurrence of seizure and/or stroke-like episode, as well as classic biomarkers (i.e., cerebral lactic acidosis, depleted N-acetylaspartate (NAA)), have been linked to neuropsychological deficit and trigger the developmental cascade of neurodegeneration affecting posterior prior to anterior brain regions. While a pattern of global deterioration has been reported, systematic examination in a large MELAS cohort has not been conducted.

Objective: First, we examined verbal and visual memory function and its relationship to brain metabolites (lactate, NAA) in individuals with MELAS. Second, we hypothesized ...

Promoting Clinical Breast Evaluations In A Lower Middle–Income Country Setting: An Approach Toward Achieving A Sustainable Breast Health Program, Roziya Buribekova, Irina Shukurbekova, Surayo Ilnazarova, Nekruz Jamshevov, Guldarbogh Sadonshoeva, Saleem Sayani, Aliya Aminmuhammad, Farin Amersi, Sheemain Asaria, Mansoor Saleh, Zohray Talib

Medical College Documents

PURPOSE:
To promote a systems-based approach for the early detection and downstaging of breast cancer at presentation in the remote mountainous region of Gorno Badakhshan Autonomous Oblast (GBAO), Tajikistan, by introducing breast cancer awareness into the community and training health care professionals in clinical breast evaluation (CBE).
METHODS:
Through a public-private partnership between the Ministry of Health, the Aga Khan Health Services, Tajikistan, and the Aga Khan Health Board, we organized breast cancer screening in the community and trained family medicine doctors (FMDs) and family medicine nurses (FMNs) in CBE. We identified and trained CBE master trainers, who, in turn ...

Lafora Disease Masquerading As Hepatic Dysfunction, Faisal Inayat, Waqas Ullah, Hanan T. Lodhi, Zarak H. Khan, Ghulam Ilyas, Nouman Safdar Ali, Hafez Mohammad A. Abdullah

Abington Hospital Papers

Lafora disease is fatal intractable progressive myoclonic epilepsy. It is frequently characterized by epileptic seizures, difficulty walking, muscle spasms, and dementia in late childhood or adolescence. We chronicle here an unusual case of an asymptomatic young male soccer player who presented with elevated liver enzymes. Neurological examination was unremarkable. The diagnostic workup for hepatitis, infectious etiologies, autoimmune disorders, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, and other related diseases was inconclusive. He subsequently underwent an uneventful percutaneous liver biopsy. Based on the pathognomonic histopathological findings, Lafora disease was considered the likely etiology. The present study is a unique illustration of ...

Prediction Of Preterm Birth With And Without Preeclampsia Using Mid-Pregnancy Immune And Growth-Related Molecular Factors And Maternal Characteristics, Laura L. Jelliffe-Pawlowski, Larry Rand, Bruce Bedell, Rebecca J. Baer, Scott P. Oltman, Mary E. Norton, Gary M. Shaw, David K. Stevenson, Jeffrey C. Murray, Kelli K. Ryckman

Stead Family Department of Pediatrics Publications

OBJECTIVE: To evaluate if mid-pregnancy immune and growth-related molecular factors predict preterm birth (PTB) with and without (±) preeclampsia.

STUDY DESIGN: Included were 400 women with singleton deliveries in California in 2009-2010 (200 PTB and 200 term) divided into training and testing samples at a 2:1 ratio. Sixty-three markers were tested in 15-20 serum samples using multiplex technology. Linear discriminate analysis was used to create a discriminate function. Model performance was assessed using area under the receiver operating characteristic curve (AUC).

RESULTS: Twenty-five serum biomarkers along with maternal age80% of women with PTB ± preeclampsia with best performance in women with ...

Review Of Karyotypic Data From Low Grade Glial Brain Tumors, Specifically Pilocytic Astrocytomas, And Correlation Of Genetic Aberrations With Tumor Recurrence., Linda D. Cooley, Scott C. Smith, Lisa Warren, Melissa Gener, Kevin Ginn, John Herriges

Posters

Abstract: Brain tumors are the most common solid tumor of childhood. Approximately 50% of pediatric CNS tumors are low grade gliomas (WHO grade I or II) and Pilocytic astrocytoma (PA) is the most common accounting for 33% of all gliomas in children 0-14 years and ~18% of all childhood brain tumors. Prognosis with this slow-growing tumor is excellent; 10 year overall survival of ~95%. However, event free survival averages ~50%. Patient age and extent of tumor resection are key prognostic factors; tumor location and size impact resection and outcome. Histopathological features indicate PA is a benign tumor and rarely are ...

Improving The Sensitivity Of Real-Time Pcr Detection Of Group B Streptococcus Using Consensus Sequence-Derived Oligonucleotides, Ameneh Khatami, Tara M. Randis, Anna Chamby, Thomas A. Hooven, Margaret Gegick, Evan Suzman, Brady A'Hearn-Thomas, Andrew P. Steenhoff, Adam J. Ratner

Stead Family Department of Pediatrics Publications

Group B Streptococcus (GBS) is a perinatal pathogen and an emerging cause of disease in adults. Culture-independent GBS detection relies on polymerase chain reaction (PCR) of conserved genes, including sip. We demonstrate suboptimal sensitivity of the existing sip PCR strategy and validate an improved method based on consensus sequences from >100 GBS genomes.

A Humanized Hypertrophic Cardiomyopathy Model To Elucidate Molecular Mechanism In Disease Pathology, Ragavi Vijayakumar, Maxine Hong

The International Student Science Fair 2018

Hypertrophic cardiomyopathy (HCM), that clinically manifests as an enlarged heart is a highly prevalent cardiac disorder with propensity towards arrhythmia-induced sudden cardiac death. The mechanism of HCM remains poorly defined, necessitating further understanding of the disease for improved therapeutic strategies. As it is challenging to obtain cardiac biopsies from human subjects, using induced pluripotent stem cells technology, we generated cardiomyocytes (CMs) in a dish from HCM patients. These HCM-CMs presented the clinical manifestation in that they were significantly larger in size in comparison to control (healthy)-CMs. Furthermore, gene expression profiling of cardiac ion channels revealed increased transcripts encoding for ...

Congenital Heart Defects And Ciliopathies Associated With Renal Phenotypes, George C. Gabriel, Gregory J. Pazour, Cecilia W. Lo

Open Access Articles

Congenital heart disease (CHD) is one of the most common birth defects, and recent studies indicate cilia-related mutations play a central role in the genetic etiology of CHD. As cilia are also known to have important roles in kidney development and disease, it is not surprising that renal anomalies were found to be enriched among CHD mutant mice recovered in a large-scale mouse forward genetic screen. Indeed 42% of mutations identified to cause both CHD and renal anomalies were cilia-related. Many of these cilia mutations comprise cilia transition zone or inversin compartment components, consistent with the known role of these ...

Apoe And Alzheimer’S Disease: Neuroimaging Of Metabolic And Cerebrovascular Dysfunction, Jason A. Brandon, Brandon C. Farmer, Holden C. Williams, Lance A. Johnson

Physiology Faculty Publications

Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for late onset Alzheimer’s Disease (AD), and is associated with impairments in cerebral metabolism and cerebrovascular function. A substantial body of literature now points to E4 as a driver of multiple impairments seen in AD, including blunted brain insulin signaling, mismanagement of brain cholesterol and fatty acids, reductions in blood brain barrier (BBB) integrity, and decreased cerebral glucose uptake. Various neuroimaging techniques, in particular positron emission topography (PET) and magnetic resonance imaging (MRI), have been instrumental in characterizing these metabolic and vascular deficits associated with this important AD risk factor ...

Integration Of Complementary And Alternative Medicine Into The Healthcare System In The United States, Nikki Lu

Global Honors Theses

Chronic diseases are a prevalent issue around the world and chronic diseases are hard to prevent due to various systemic factors in the healthcare system. This paper mainly focused on socioeconomic issues and highlighted a few systemic factors in the US healthcare system. These factors have created various health disparities, inequities among socially constructed groups, and financial expenditures in the US healthcare system. Socioeconomic factors significantly impact the health and healthcare among socially constructed groups. Additionally, in this paper there are current approaches in addressing these healthcare factors such as social determinants of health and precision medicine as well as ...

Genes Associated With Mandibular Prognathism In The Chinese Population, Jacqueline Payne, Marie Tolarova M.D., Ph.D., D.Sc.

Excellence Day

Mandibular prognathism (MP) is the relationship of the mandible anteriorly positioned in relation to the cranial base. The prevalence of MP in Asians is estimated to be 15%, whereas American and European descent exhibit a 5% prevalence. Orthodontic treatment is lengthy and challenging, and severe cases require surgical intervention. However, when a treatment is planned well, the outcomes are predominantly successful. It has been known that genetics are involved in the etiology of prognathism and that greater genetic contribution corresponds to greater challenges to treatment. Thus, there is a desire to determine genes involved in the etiology of prognathism.

Banning Abortion In Cases Of Down Syndrome: Important Lessons For Advances In Genetic Diagnosis, Rebecca Reingold, Lawrence O. Gostin

Georgetown Law Faculty Publications and Other Works

In December 2017, Ohio passed into law legislation that prohibited physicians from performing abortions if the pregnant woman’s decision was influenced by her belief that the fetus has Down syndrome. Physicians who perform abortions in these cases would face fourth-degree felony charges and revocation of their medical license. No other state bans abortion specifically for Down syndrome, but several ban abortions in cases of genetic diseases. Lower courts have struck down most such laws, holding they violate the constitutional rights of women. In February 2018, a federal district court judge blocked enforcement of Ohio’s law pending a final ...

Insurance Coverage Policies For Pharmacogenomic And Multi-Gene Testing For Cancer, Christine Y. Lu, Stephanie Loomer, Rachel Ceccarelli, Kathleen M. Mazor, James Sabin, Ellen Wright Clayton, Geoffrey S. Ginsburg, Ann Chen Wu

Open Access Articles

Insurance coverage policies are a major determinant of patient access to genomic tests. The objective of this study was to examine differences in coverage policies for guideline-recommended pharmacogenomic tests that inform cancer treatment. We analyzed coverage policies from eight Medicare contractors and 10 private payers for 23 biomarkers (e.g., HER2 and EGFR) and multi-gene tests. We extracted policy coverage and criteria, prior authorization requirements, and an evidence basis for coverage. We reviewed professional society guidelines and their recommendations for use of pharmacogenomic tests. Coverage for KRAS, EGFR, and BRAF tests were common across Medicare contractors and private payers, but ...

Somatic Mutation Detection In Leukemia-Derived Circulating Dna: Utility In Monitoring Clonal Dynamics And Disease Response In Pediatric Acute Lymphoblastic Leukemia, Sarah Hisham Abdelaziz Youssef

Theses and Dissertations (ETD)

Despite the improved outcome associated with current treatment strategies ofpediatric acute lymphoblastic leukemia (ALL), relapse still represents a major challenge. Pediatric ALL demonstrates branched evolution in response to selective pressure exerted by therapy; relapse founder clones emerge from pre-leukemic clones or minor subclones present at diagnosis. It is hence crucial to develop biomarkers capable of tracking subclones throughout therapy. Current practices for monitoring disease response in leukemia rely on the analysis of BM biopsy sample at specific time points throughout therapy. Not only the invasiveness of the BM biopsy hinders the sequential sampling, but also, the currently implied techniques are ...

Optimization Of Braf V600 Assay As A 2-Step Real-Time Pcr Protocol, Mimi Phuong

Master's Theses and Capstone Projects

The QClamp® BRAF Codon Specific Mutation Detection Kit is a real-time PCR assay for the detection of somatic mutations in codon 600 Valine at exon 15 in the BRAF gene which encodes the serine/threonine protein kinase, using purified DNA. The V600E mutation is the most common BRAF gene mutation found in human cancers. This mutation leads to production of a BRAF protein that is abnormally active, which disrupts regulation of cell growth and division. Mutations in this gene have been found in cancers, including non-Hodgkin lymphoma, colorectal cancer, malignant melanoma, papillary thyroid carcinoma, non-small-cell lung carcinoma, gastric cancer, and ...

Dystrophic Calcifications Point The Way-Unusual And Early Diagnostic Clue Of Conradi-Hünermann-Happle Syndrome, Kenneth Yu, Alexander T. Reid, Stephanie J T Chen, Rajiv M. Patel, Steven M. Donn, Johann E. Gudjonsson, Lori Lowe

Stead Family Department of Pediatrics Publications

No abstract provided.

Effect Of Trinucleotide Repeats In The Huntington's Gene On Intelligence, Jessica K. Lee, Amy Conrad, Eric Epping, Kathy Mathews, Vincent Magnotta, Jeffrey D. Dawson, Peg Nopoulos

Stead Family Department of Pediatrics Publications

BACKGROUND: Huntington's Disease (HD) is caused by an abnormality in the HTT gene. This gene includes trinucleotide repeats ranging from 10 to 35, and when expanded beyond 39, causes HD. We previously reported that CAG repeats in the normal range had a direct and beneficial effect on brain development with higher repeats being associated with higher cognitive function. The current study now expands this line of inquiry to evaluate the effects of CAG repeat throughout the entire spectrum of repeats from 15 to 58.

METHODS: We evaluated brain function in children ages 6-18 years old. DNA samples were processed ...

Surfactant Deficiency Syndrome In An Infant With A C-Terminal Frame Shift In Abca3: A Case Report, Nour Akil, Anthony J. Fischer

Stead Family Department of Pediatrics Publications

Deficiency in ATP binding cassette A3 (ABCA3) causes neonatal respiratory distress, hypoxemic respiratory failure, and interstitial lung disease. ABCA3 transports phospholipids into the lamellar bodies of type II alveolar cells, a critical step in alveolar surfactant production. We report a term infant with ABCA3 surfactant deficiency syndrome with the E292V (c.875A>T; p.Glu292Val) mutation in trans with a novel C-terminal frame shift mutation (c.4938delC; p.Met1647fs). This mutation removes the final 58 amino acids and substitutes 33 incorrect amino acids. The frame shift spares membrane spanning and nucleotide binding domains, but disrupts a highly conserved C-terminal domain ...

Designer Babies: A Paired Analysis Of The Technological Advances And Ethical Implications Of Genetic Selection, Alexandra Schmerge

Student research

No abstract provided.

Hutchinson-Gilford Progeria Syndrome Vascular Pathology: A Focused Review, Danielle M. Eschedor

Senior Honors Theses

Hutchinson-Gilford Progeria is an accelerated aging disorder caused by a de novo point mutation in the LMNA gene which codes for an intermediate filament of the nuclear lamina called lamin A. The point mutation at c.1824C>T causes a 50-amino-acid deletion that removes the binding site for Zmpste24, a metalloprotease responsible for defarnesylating prelamin A and producing mature lamin A. Without the ability to be defarnesylated, the mutated protein, called progerin, is more lipophilic and has a myriad of cytotoxic effects. As cardiovascular disease is the most common cause of death in HGPS patients, it is important for both ...