A5082184763- Ocular Oncology and Treatments
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Cutaneous Melanoma Detection and Management
- Cancer Genomics and Diagnostics
- Retinal Development and Disorders
- Prenatal Screening and Diagnostics
- Cell Adhesion Molecules Research
- Genetic Syndromes and Imprinting
- Neuroblastoma Research and Treatments
- Cancer-related gene regulation
- Connective tissue disorders research
- Vascular Anomalies and Treatments
- Pancreatic function and diabetes
- Hedgehog Signaling Pathway Studies
- BRCA gene mutations in cancer
- Metabolism and Genetic Disorders
- Vascular Malformations and Hemangiomas
- Advanced biosensing and bioanalysis techniques
- Tracheal and airway disorders
- Hemophilia Treatment and Research
- DNA and Nucleic Acid Chemistry
- Cardiac Ischemia and Reperfusion
- Corneal Surgery and Treatments
University of Pennsylvania
2016-2025
California University of Pennsylvania
2003-2024
Western University
2024
Thomas Jefferson University
1989-2021
Wills Eye Hospital
2019-2021
Children's Hospital of Philadelphia
2001-2020
University of Pennsylvania Health System
2019
Christie's
2019
Bayer (Switzerland)
2012
Regeneron (United States)
2012
<h3>Background</h3> HHT is an autosomal dominant disease with estimated prevalence of at least 1/5000 which can frequently be complicated by the presence clinically significant arteriovenous malformations in brain, lung, gastrointestinal tract and liver. under-diagnosed families may unaware available screening treatment, leading to unnecessary stroke life-threatening hemorrhage children adults. <h3>Objective</h3> The goal this international guidelines process was develop evidence-informed...
To define the incidence of BRCA1 mutations among patients seen in clinics that evaluate risk breast cancer, we analyzed DNA samples from women this setting and constructed probability tables to provide estimates likelihood finding a mutation individual families.
Several techniques have recently been developed to detect single-base mismatches in DNA heteroduplexes that contain one strand of wild-type and mutated DNA. Here we tested the hypothesis an appropriate system mildly denaturing solvents can amplify tendency produce conformational changes, such as bends double helix, thereby increase differential migration homoduplexes during gel electrophoresis. The best separations were obtained with a standard 6% polyacrylamide polymerized 10% ethylene...
Hypoglycemia due to congenital hyperinsulinism (HI) is caused by mutations in 9 genes. Our objective was correlate genotype with phenotype 417 children HI. Mutation analysis carried out for the ATP-sensitive potassium (KATP) channel genes (ABCC8 and KCNJ11), GLUD1, GCK supplemental screening of rarer genes, HADH, UCP2, HNF4A, HNF1A, SLC16A1. Mutations were identified 91% (272 298) diazoxide-unresponsive probands (ABCC8, KCNJ11, GCK), 47% (56 118) diazoxide-responsive HNF1A). In diffuse...
<b>Background:</b> Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease exhibiting multifocal vascular telangiectases and arteriovenous malformations. The majority of cases are caused by mutations in either the endoglin (<i>ENG</i>) or activin receptor-like kinase 1 (<i>ALK1, ACVRL1)</i> genes; both members transforming growth factor (TGF)-β pathway. Mutations <i>SMAD4</i>, another TGF-β pathway member, seen patients with combined syndrome juvenile polyposis (JP) HHT...
Congenital hyperinsulinism is a condition of dysregulated insulin secretion often caused by inactivating mutations the ATP-sensitive K+ (KATP) channel in pancreatic β cell. Though most disease-causing 2 genes encoding KATP subunits, ABCC8 (SUR1) and KCNJ11 (Kir6.2), are recessively inherited, some cases dominantly inherited have been reported. To better understand differences between mutations, we identified characterized 16 families with 14 different including total 33 affected individuals....
BACKGROUND. Fibrodysplasia ossificans progressiva is a rare and disabling genetic condition characterized by congenital malformation of the great toes progressive heterotopic ossification in specific anatomic patterns. Most patients with fibrodysplasia are misdiagnosed early life before appearance undergo diagnostic procedures that can cause lifelong disability. Recently, was identified, definitive testing for now available ossification. METHODS. We recently evaluated 7 children diagnosis...
Purpose.: Somatic mutations in GNAQ, GNA11, SF3B1, EIF1AX, and BAP1 have been identified uveal melanoma (UM). The aim of this study was to determine whether these genes primary tumors were associated with metastases individuals diagnosed UM. Methods.: A total 63 UM cases who developed a metastasis within 48 months treatment 53 controls metastasis-free over similar time period selected for the study. Primary screened BAP1. association tumor characteristics, chromosome 3 copy number,...
Reducing body myopathy (RBM) is a rare disorder causing progressive muscular weakness characterized by aggresome-like inclusions in the myofibrils. Identification of genes responsible for RBM traditional genetic approaches has been impossible due to frequently sporadic occurrence affected patients and small family sizes. As an alternative approach gene identification, we used laser microdissection intracytoplasmic identified patient muscle biopsies, followed nanoflow liquid...
Abstract Juvenile polyposis (JP) and hereditary hemorrhagic telangiectasia (HHT) are clinically distinct diseases caused by mutations in SMAD4 BMPR1A (for JP) endoglin ALK1 HHT). Recently, a combined syndrome of JP–HHT was described that is also . Although both JP mutations, possible genotype:phenotype correlation noted as all the patients were clustered COOH‐terminal MH2 domain protein. If valid, this would provide molecular explanation for phenotypic differences, well pre‐symptomatic...
// Justina McEvoy 1,* , Panduka Nagahawatte 2,* David Finkelstein 2 Jennifer Richards-Yutz 6 Marcus Valentine 13 Jing Ma 14 Charles Mullighan Guangchun Song Xiang Chen Matthew Wilson 4 Rachel Brennan 12 Stanley Pounds 3 Jared Becksfort Robert Huether Lu 7 S. Fulton 7,8 Lucinda L. Xin Hong J. Dooling Kerri Ochoa Elaine R. Mardis 7,8,9 Richard K.Wilson 7,8,10 John Easton Jinghui Zhang James Downing Arupa Ganguly 5,6,* and Michael A. Dyer 1,4,11 for the St. Jude Children’s Research...
<h3>Background</h3> Congenital hyperinsulinism (HI) can have monogenic or syndromic causes. Although HI has long been recognised to be common in children with Beckwith–Wiedemann syndrome (BWS), the underlying mechanism is not known. <h3>Methods</h3> We characterised clinical features of both and BWS/11p overgrowth spectrum, evaluated contribution KATP channel mutations molecular pathogenesis their assessed associated BWS. <h3>Results</h3> identified 28 from 1997 2014. Mosaic paternal...
Abstract Beckwith‐Wiedemann syndrome (BWS) is the most common epigenetic overgrowth and cancer predisposition disorder. Due to both varying molecular defects involving chromosome 11p15 tissue mosaicism, patients can present with a variety of clinical features, leading newly defined spectrum (BWSp). The BWSp be further divided into three subsets patients: those presenting classic isolated lateralized (ILO) not fitting previous two categories, termed atypical BWSp. Previous reports BWS have...
Abstract Background Rapid spread of SARS-CoV-2 has led to a global pandemic, resulting in the need for rapid assays allow diagnosis and prevention transmission. Reverse transcription-polymerase chain reaction (RT-PCR) provides gold standard assay RNA, but instrument costs are high supply chains potentially fragile, motivating interest additional methods. transcription loop-mediated isothermal amplification (RT-LAMP) an alternative that uses orthogonal often less expensive reagents without...
Mutations in the two genes for type I collagen (COL1A1 or COL1A2) cause osteogenesis imperfecta (OI), a heritable disease characterized by moderate to extreme brittleness of bone early life. Here we show that 52-year-old postmenopausal woman with severe osteopenia and compression fracture thoracic vertebra had mutation gene alpha 2(I) chain (COL1A2) similar mutations OI. cDNA was prepared from woman's skin fibroblast RNA assayed presence treating DNA heteroduplexes carbodiimide. The results...
Hereditary hemorrhagic telangiectasia (HHT; Osler-Weber-Rendu disease) is an autosomal dominant disease characterized by arteriovenous malformations ranging from cutaneous and mucous membrane telangiectasias to more severe pulmonary, gastrointestinal, cerebral (AVMs). Acute complications bleeding or pulmonary shunting may be catastrophic. However, when diagnosed early, the can usually prevented. Mutations in two genes, Endoglin (ENG) activin receptor-like kinase 1 (ACVRL1 ALK1) have been...
The hyperinsulinism/hyperammonemia (HI/HA) syndrome is a form of congenital hyperinsulinism in which affected children have recurrent symptomatic hypoglycemia together with asymptomatic, persistent elevations plasma ammonium levels. We shown that the disorder caused by dominant mutations mitochondrial enzyme, glutamate dehydrogenase (GDH), impair sensitivity to allosteric inhibitor, GTP. In 65 HI/HA probands screened for GDH mutations, we identified 19 (29%) who had new domain, encoded exons...
<h3>Objective</h3> To evaluate the feasibility of genetic testing uveal melanoma using fine-needle aspiration biopsy (FNAB). <h3>Methods</h3> We reviewed clinical records all patients Ocular Oncology Service at Wills Eye Hospital with diagnosis who underwent FNAB for chromosome 3 status between November 1, 2005, and March 2006. The was performed immediately before plaque radiotherapy. specimens analysis DNA amplification microsatellite assay to determine presence monosomy 3. <h3>Results</h3>...
Congenital hyperinsulinism (CHI) is a disease characterized by persistent insulin secretion despite severe hypoglycemia. Mutations in the pancreatic ATP-sensitive K(+) (K(ATP)) channel proteins sulfonylurea receptor 1 (SUR1) and Kir6.2, encoded ABCC8 KCNJ11, respectively, most common cause of disease. Many mutations SUR1 render unable to traffic cell surface, thereby reducing function. Previous studies have shown that for some trafficking mutants, defects could be corrected treating cells...