Sarah E. Sheppard
A5047941457- Vascular Malformations and Hemangiomas
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Genomics and Rare Diseases
- Lymphatic System and Diseases
- Cancer-related gene regulation
- Genomic variations and chromosomal abnormalities
- Hedgehog Signaling Pathway Studies
- Congenital Heart Disease Studies
- Prenatal Screening and Diagnostics
- Tumors and Oncological Cases
- Skin and Cellular Biology Research
- Vascular Tumors and Angiosarcomas
- Epigenetics and DNA Methylation
- Biochemical and Molecular Research
- Genetic and Kidney Cyst Diseases
- Protein Tyrosine Phosphatases
- Congenital heart defects research
- RNA Research and Splicing
- Lymphatic Disorders and Treatments
- Chromatin Remodeling and Cancer
- Genomics and Chromatin Dynamics
- RNA regulation and disease
- Electronic Health Records Systems
- Dermatological and Skeletal Disorders
Children's Hospital of Philadelphia
2018-2025
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2022-2025
Peterborough City Hospital
2025
University of Pennsylvania
2018-2024
Genomics (United Kingdom)
2023
University of Wisconsin–Madison
2022
University of Massachusetts Chan Medical School
2013-2017
George Eliot Hospital
2009
George Eliot Hospital NHS Trust
2009
IIT@MIT
2007
22q11.2 deletion syndrome (22q11.2DS) is a disorder caused by recurrent, chromosome‐specific, low copy repeat (LCR)–mediated copy‐number losses of chromosome 22q11. The Children's Hospital Philadelphia has been involved in the clinical care individuals with what now known as 22q11.2DS since our initial report association DiGeorge 1982. We reviewed medical records on continuously growing longitudinal cohort 1,421 patients molecularly confirmed from 1992 to 2018. Most are Caucasian and older...
Report7 September 2020Open Access Transparent process Kaposiform lymphangiomatosis effectively treated with MEK inhibition Jessica B Foster Corresponding Author [email protected] orcid.org/0000-0002-8001-5960 Division of Oncology, Children's Hospital Philadelphia, PA, USA Search for more papers by this author Dong Li Center Applied Genomics, Michael E March Sarah Sheppard Divisions Human Genetics and Pulmonary Medicine, Denise M Adams Vascular Anomalies Center, Boston Hospital, Boston, MA,...
Abstract Wiedemann‐Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized intellectual disability hypertrichosis. We performed a retrospective, multicenter, observational study of 104 individuals with WSS from five continents to characterize the clinical molecular spectrum diverse populations, identify physical features that may be more prevalent White versus Black Indigenous People Color individuals, delineate genotype–phenotype...
Germline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) are the most frequent, recurrent monogenic of cerebral palsy (CP). We investigated range clinical phenotypes owing to disruptions determine association between NEDSDV CP.Genetic information from 404 individuals collectively 392 pathogenic were ascertained for study. From these, detailed 52 previously unpublished collected combined 68 published...
Central conducting lymphatic anomaly (CCLA) due to congenital maldevelopment of the lymphatics can result in debilitating and life-threatening disease with limited treatment options. We identified 4 individuals CCLA, lymphedema, microcystic malformation pathogenic, mosaic variants KRAS. To determine functional impact these identify a targeted therapy for individuals, we used primary human dermal endothelial cells (HDLECs) zebrafish larvae model dysplasia. Expression p.Gly12Asp p.Gly13Asp...
Central conducting lymphatic anomaly (CCLA) is a complex characterized by abnormalities of the central lymphatics and may present with nonimmune fetal hydrops, chylothorax, chylous ascites, or lymphedema. CCLA has historically been difficult to diagnose treat; however, recent advances in imaging, such as dynamic contrast magnetic resonance lymphangiography, genomics, deep sequencing utilization cell-free DNA, have improved diagnosis refined both genotype phenotype. Furthermore, vitro vivo...
Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting vessels including thoracic duct and cisterna chyli, presenting as chylothorax, pleural effusions, chylous ascites, lymphedema, is a severe disorder often resulting in fetal or perinatal demise. Although pathogenic variants RAS/mitogen activated protein kinase (MAPK) signaling pathway components have been documented some patients with CCLA, genetic etiology remains uncharacterized most cases....
Complex lymphatic anomalies are debilitating conditions characterized by aberrant development of the vasculature (lymphangiogenesis). Diagnosis is typically made history, examination, radiology, and histologic findings. However, there significant overlap between conditions, making accurate diagnosis difficult. Recently, genetic analysis has been offered as an additional diagnostic modality. Here, we describe four cases complex anomalies, all with PIK3CA variants but varying clinical...
Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is a germline vascular dysplasia that typically characterized by cutaneous capillary malformations and central nervous system arteriovenous (AVM). We report an atypical presentation of CM-AVM2 featuring giant coronary fistula. A 22-day-old male exhibited cardiac murmur, leading to the discovery large fistula from left circumflex artery. The patient developed eye exophthalmos due left-sided basilar pontomesencephalic vein...
ABSTRACT Our study aimed to evaluate cognitive function in individuals with genetic skin disorders involving neuroectoderm ( n = 8) compared only ectoderm or mesoderm 16) involvement. We hypothesized that neuroectodermal involvement would result poorer neurocognitive performance. A prospective, cross‐sectional pilot of 24 participants evaluated cognition, adaptive skills, behavior, and quality life (QoL) using neurodevelopmental tests. Participants' characteristics outcomes interest were...
Cancer treatment services face considerable pressures across the SACT pathway. The availability of a subcutaneous formulation Tecentriq (atezolizumab) presents opportunities to decentralise delivery new venues. With sufficient workforce training and flexibility, decentralisation could produce lasting improvement in outcomes. Six case studies are presented highlighting successful examples service using (SC) atezolizumab, covering their impacts on patients.
PurposeHearing loss (HL) is the most common sensory disorder in children. Prompt molecular diagnosis may guide screening and management, especially syndromic cases when HL single presenting feature. Exome sequencing (ES) an appealing diagnostic tool for as genetic causes are highly heterogeneous.MethodsES was performed on a prospective cohort of 43 probands with HL. Sequence data were analyzed primary secondary findings. Capture coverage analysis genes variants associated HL.ResultsThe rate...
Abstract Genetic variants in chromatin regulators are frequently found neurodevelopmental disorders, but their effect disease etiology is rarely determined. Here, we uncover and functionally define pathogenic the modifier EZH1 as cause of dominant recessive disorders 19 individuals. encodes one two alternative histone H3 lysine 27 methyltransferases PRC2 complex. Unlike other subunits, which involved cancers developmental syndromes, implication human development largely unknown. Using...
Abstract Motivation: 3′ end processing is important for transcription termination, mRNA stability and regulation of gene expression. To identify ends, most techniques use an oligo-dT primer to construct deep sequencing libraries. However, this approach can lead identification artifactual polyadenylation sites due internal priming in homopolymeric stretches adenines. Although heuristic filters have been applied these cases, they typically result a high proportion both false-positive -negative...
CREBBP loss‐of function variants cause Rubinstein–Taybi syndrome (RTS). There have been two separate reports of patients with missense in exon 30 or 31 individuals lacking the characteristic facial and limb dysmorphism associated RTS. Frequent features this condition include variable intellectual disability, short stature, autistic behavior, microcephaly, feeding problems, epilepsy, recurrent upper airway infections, mild hearing impairment. We report three further de novo variants. The...
Patients with rare diseases often experience prolonged diagnostic delays. Ordering appropriate genetic tests is crucial yet challenging, especially for general pediatricians without expertise. Recent American College of Medical Genetics (ACMG) guidelines embrace early use exome sequencing (ES) or genome (GS) conditions like congenital anomalies developmental delays while still recommend gene panels patients exhibiting strong manifestations a specific disease. Recognizing the difficulty in...
Pathogenic variants in