A5062304510- Muscle Physiology and Disorders
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Cardiomyopathy and Myosin Studies
- RNA Research and Splicing
- RNA modifications and cancer
- Hereditary Neurological Disorders
- Myasthenia Gravis and Thymoma
- Genomics and Rare Diseases
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Metabolism and Genetic Disorders
- Cerebral Palsy and Movement Disorders
- Glycogen Storage Diseases and Myoclonus
- Botulinum Toxin and Related Neurological Disorders
- Nuclear Structure and Function
- Lysosomal Storage Disorders Research
- Japanese History and Culture
- Philippine History and Culture
- BRCA gene mutations in cancer
- Peripheral Neuropathies and Disorders
- Muscle activation and electromyography studies
- Adipose Tissue and Metabolism
- Thyroid and Parathyroid Surgery
University of Minnesota
2021-2025
University of Minnesota Medical Center
2021-2025
Tempus Labs (United States)
2022-2025
University of Florida
2015-2024
Guy's and St Thomas' NHS Foundation Trust
2024
Florida College
2014-2023
University of South Carolina
2023
Boston Children's Hospital
2012-2022
Harvard University
2011-2022
University of Michigan
2016-2022
Transcriptome sequencing improves the diagnostic rate for Mendelian disease in patients whom genetic analysis has not returned a diagnosis.
The primary muscle disorders are a diverse group of diseases caused by various defective structural proteins, abnormal signaling molecules, enzymes and proteins involved in posttranslational modifications, other mechanisms. Although there is increasing clarification the aberrant cellular processes responsible for these conditions, decisive factors secondary pathogenic cascades still mainly obscure. Given emerging roles microRNAs (miRNAs) modulation phenotypes, we searched miRNAs regulated...
Mycobacterium tuberculosis (M.tb) survives in macrophages part by limiting phagosome–lysosome (P-L) fusion. M.tb mannose-capped lipoarabinomannan (ManLAM) blocks phagosome maturation. The pattern recognition mannose receptor (MR) binds to the ManLAM caps and mediates phagocytosis of bacilli human macrophages. Using quantitative electron confocal microscopy, we report that engagement MR during phagocytic process is a key step P-L fusion microspheres was significantly reduced an MR-expressing...
Prospective cohort study to characterize the clinical features and course of spinal muscular atrophy type I (SMA-I).Patients were enrolled at 3 sites followed for up 36 months with serial clinical, motor function, laboratory, electrophysiologic outcome assessments. Intervention was determined by published standard care guidelines. Palliative options offered.Thirty-four 54 eligible subjects SMA-I (63%) 50% these completed least 12 follow-up. The median age reaching combined endpoint death or...
Recommendations from the American College of Medical Genetics and Genomics Association for Molecular Pathology (ACMG/AMP) interpreting sequence variants specify use computational predictors as "supporting" level evidence pathogenicity or benignity using criteria PP3 BP4, respectively. However, score intervals defined by tool developers, ACMG/AMP recommendations that require consensus multiple predictors, lack quantitative support. Previously, we described a probabilistic framework quantified...
To characterize the natural history of spinal muscular atrophy type 2 and 3 (SMA 2/3) beyond 1 year to report data on clinical biological outcomes for use in trial planning.
Corticosteroids improve strength and function in boys with Duchenne muscular dystrophy. However, there is uncertainty regarding the optimum regimen dosage.To compare efficacy adverse effects of 3 most frequently prescribed corticosteroid regimens dystrophy.Double-blind, parallel-group randomized clinical trial including 196 aged 4 to 7 years dystrophy who had not previously been treated corticosteroids; enrollment occurred between January 30, 2013, September 17, 2016, at 32 clinic sites 5...
Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding dystrophin, which results dysfunctional signaling pathways within muscle. Previously, we identified microRNA-486 (miR-486) as a muscle-enriched microRNA that markedly reduced muscles of dystrophin-deficient mice (Dmdmdx-5Cv mice) and DMD patient muscles. Here, determined muscle-specific transgenic overexpression miR-486 muscle Dmdmdx-5Cv serum creatine kinase levels, improved sarcolemmal integrity, fewer...
Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, abnormally centralized nuclei. Autosomal dominant CNM due to mutations in the large GTPase dynamin 2 (DNM2), mechanochemical enzyme regulating cytoskeleton membrane trafficking cells. To date, 40 families CNM-related DNM2 have been described, here we report 60 additional encompassing broad genotypic phenotypic spectrum. In total, 18...
Missense mutations in TUBB3, the gene that encodes neuronal-specific protein β-tubulin isotype 3, can cause isolated or syndromic congenital fibrosis of extraocular muscles, a form complex strabismus characterized by cranial nerve misguidance. One eight TUBB3 reported to c.1228G>A results E410K amino acid substitution directly alters kinesin motor binding site. We report detailed phenotypes unrelated individuals who harbour this de novo mutation, and thus define 'TUBB3 syndrome'. Individuals...
Mutations affecting skeletal muscle isoforms of the tropomyosin genes may cause nemaline myopathy, cap core-rod congenital fiber-type disproportion, distal arthrogryposes, and Escobar syndrome. We correlate clinical picture these diseases with novel (19) previously reported (31) mutations TPM2 TPM3 genes. Included are altogether 93 families: 53 40 mutations. Thirty distinct pathogenic variants 20 have been published or listed in Leiden Open Variant Database (http://www.dmd.nl/). Most...
<h3>Objective:</h3> To delineate optimal diagnostic and therapeutic approaches to congenital muscular dystrophy (CMD) through a systematic review analysis of the currently available literature. <h3>Methods:</h3> Relevant, peer-reviewed research articles were identified using literature search MEDLINE, EMBASE, Scopus databases. Diagnostic data from these extracted analyzed in accordance with American Academy Neurology classification evidence schemes for diagnostic, prognostic, studies....
Duchenne muscular dystrophy (DMD) is an X-linked myopathy resulting from the production of a nonfunctional dystrophin protein. MicroRNA (miRNA) are small 21- to 24-nucleotide RNA that can regulate both individual genes and entire cell signaling pathways. Previously, we identified several mRNA, muscle-enriched inflammation-induced, dysregulated in skeletal muscles DMD patients. One particularly miRNA, miR-486, significantly downregulated dystrophin-deficient mouse human muscles. miR-486...
Dystroglycan is a transmembrane glycoprotein whose interactions with the extracellular matrix (ECM) are necessary for normal muscle and brain development, disruptions of its function lead to dystroglycanopathies, group congenital muscular dystrophies showing extreme genetic clinical heterogeneity. Specific glycans bound portion dystroglycan, α-dystroglycan, mediate ECM most known dystroglycanopathy genes encode glycosyltransferases involved in glycan synthesis. POMK, which was found mutated...