A5029997151- Ocular Disorders and Treatments
- Congenital Ear and Nasal Anomalies
- Genetic Neurodegenerative Diseases
- Reconstructive Facial Surgery Techniques
- Genomics and Rare Diseases
- Neurogenetic and Muscular Disorders Research
- Hereditary Neurological Disorders
- Neurological diseases and metabolism
- Genetics and Neurodevelopmental Disorders
- Parkinson's Disease Mechanisms and Treatments
- Craniofacial Disorders and Treatments
- Intraocular Surgery and Lenses
- Neurological disorders and treatments
- Hedgehog Signaling Pathway Studies
- Retinal Development and Disorders
- Cell Adhesion Molecules Research
- Connexins and lens biology
- Autism Spectrum Disorder Research
- CRISPR and Genetic Engineering
- Renal and related cancers
- Corneal Surgery and Treatments
- Mitochondrial Function and Pathology
- Glycogen Storage Diseases and Myoclonus
- BRCA gene mutations in cancer
- Genomic variations and chromosomal abnormalities
Einstein Medical Center Philadelphia
2011-2025
University of Pennsylvania
2016-2024
Sarepta Therapeutics (United States)
2023-2024
Pennsylvania Hospital
2018-2023
University of Pennsylvania Health System
2022
Medical College of Wisconsin
2021
Children's Hospital of Wisconsin
2021
California University of Pennsylvania
2020
Children's Hospital of Philadelphia
2019
National Institute of Neurological Disorders and Stroke
2019
BMP4 loss-of-function mutations and deletions have been shown to be associated with ocular, digital, brain anomalies, but due the paucity of these reports, full phenotypic spectrum human is not clear. We screened 133 patients a variety ocular disorders for coding region or genomic deletions. were detected in two patients: patient affected SHORT syndrome anterior segment anomalies along craniofacial dysmorphism cognitive impairment. In addition this, three intragenic identified. A...
Abstract SOX2 represents a High Mobility Group domain containing transcription factor that is essential for normal development in vertebrates. Mutations are known to result spectrum of severe ocular phenotypes humans, also typically associated with other systemic defects. Ocular include anophthalmia/microphthalmia (A/M), optic nerve hypoplasia, coloboma and eye anomalies. We screened 51 unrelated individuals A/M identified mutations the coding region gene 10 individuals. Seven novel...
The OTX2 homeobox-containing transcription factor gene was shown to play a key role in the development of head structures vertebrates. In humans, mutations result anophthalmia/microphthalmia (A/M) often associated with systemic anomalies. We screened 52 unrelated individuals affected A/M and identified disease-causing variants four families (8%), higher frequency than previously reported. All are predicted truncation normal protein sequence, consistent reported mechanisms; three changes...
Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) eight unrelated families. Four these are nonsense, two frame-shift, missense. The missense both second Thyroglobulin Type-1...
The major active retinoid, all-trans retinoic acid, has long been recognized as critical for the development of several organs, including eye. Mutations in STRA6, gene encoding cellular receptor vitamin A, patients with Matthew–Wood syndrome and anophthalmia/microphthalmia (A/M), have previously demonstrated importance retinol metabolism human eye disease. We used homozygosity mapping combined next-generation sequencing to interrogate anophthalmia microphthalmia new causative genes....
Vax1 and Vax2 have been implicated in eye development the closure of choroid fissure mice zebrafish. We sequenced coding exons VAX1 VAX2 70 patients with anophthalmia/microphthalmia (A/M). In VAX1, we observed homozygosity for two successive nucleotide substitutions c.453G>A c.454C>A, predicting p.Arg152Ser, a proband Egyptian origin microphthalmia, small optic nerves, cleft lip/palate, corpus callosum agenesis. This mutation affects an invariant residue homeodomain was absent from 96...
Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology unknown in more than 50% of patients. We used exome sequencing with ACE Exome(TM) (Personalis, Inc; 18 cases) and UCSF Genomics Core (21 to sequence 28 patients A/M four varied developmental eye defects. In A/M, we identified de novo mutations three (OTX2, p.(Gln91His), RARB, p.Arg387Cys GDF6, p.Ala249Glu) inherited STRA6 two defects, female cataracts cardiomyopathy had COL4A1 mutation,...
The field of epilepsy genetics is advancing rapidly and emerging as a frequent indication for diagnostic genetic testing. Within the larger ClinGen framework, Epilepsy Gene Curation Expert Panel tasked with connecting two increasingly separate fields: domain traditional clinical epileptology, its own established language classification criteria, evolving area testing that adheres to formal criteria gene variant curation. We identify critical components unique curation effort, including: (a)...
Abstract FOXE3 forkhead transcription factor is essential to lens development in vertebrates. The eyes of Foxe3/foxe3 ‐deficient mice and zebrafish fail develop normally. In humans, autosomal dominant recessive mutations have been associated with variable phenotypes including anterior segment anomalies, cataract, microphthalmia. We undertook sequencing 116 probands a spectrum ocular defects ranging from dysgenesis cataract anophthalmia/microphthalmia. Recessive were found four 26 affected...
Abstract Background The size of the vertebrate eye and retina is likely to be controlled at several stages embryogenesis by mechanisms that affect cell cycle length as well survival. A mutation in zebrafish out sight ( ) locus results a particularly severe reduction size. goal this study characterize m233 mutant, determine whether mutations gene cause microphthalmia humans. Results In study, we show mutant caused gdf6a gene. Despite small size, overall retinal architecture appears largely...
There have been no specific guidelines regarding which genes should be tested in the clinical setting for Parkinson's disease (PD) or parkinsonism. We evaluated types of genetic testing offered PD as first step our gene curation.
Anophthalmia and microphthalmia are important birth defects, but their pathogenesis remains incompletely understood. We studied a patient with severe unilateral who had 2.7 Mb deletion at chromosome 18q22.1 that was inherited from his mother. In-situ hybridization showed one of the deleted genes, TMX3, expressed in retinal neuroepithelium lens epithelium developing murine eye. re-sequenced TMX3 162 patients anophthalmia or microphthalmia, found two missense substitutions unrelated patients:...
Abstract The COVID‐19 pandemic rapidly changed genetic counseling services across the United States. At University of Pennsylvania (UPenn), a large academic hospital in an urban setting, nearly all (GC) visits for adult–onset disorders within Department Neurology were conducted via secure videoconferencing (telegenetics) or telephone between March and December 2020. Although telemedicine have been steadily emerging, many clinical programs, including neurogenetics program at UPenn, had not...
While genetics evaluation is increasingly utilized in adult neurology patients, its usage and efficacy are not well characterized. Here, we report our experience with 1461 consecutive patients evaluated an neurogenetics clinic at a large academic medical center between January 2015 March 2020. Of the evaluated, 1215 were referred for purposes of identifying genetic diagnosis undiagnosed condition, 90.5% whom underwent testing. The modalities testing varied across referral diagnostic...
ABSTRACT Background Monogenic causes of isolated dystonia are heterogeneous. Assembling cohorts affected individuals sufficiently large to establish new gene–disease relationships can be challenging. Objective We sought expand the catalogue monogenic etiologies for dystonia. Methods After discovery a candidate variant in multicenter exome‐sequenced cohort with dystonia, we queried online platforms and genomic data repositories worldwide identify subjects matching genotypic profiles. Results...