Alan H. Beggs
A5056568766- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Genomics and Rare Diseases
- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Cellular transport and secretion
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- RNA Research and Splicing
- Genomic variations and chromosomal abnormalities
- Cancer-related gene regulation
- Metabolism and Genetic Disorders
- Genetic Neurodegenerative Diseases
- Cellular Mechanics and Interactions
- Epigenetics and DNA Methylation
- Nuclear Structure and Function
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Cardiac Arrhythmias and Treatments
- Cardiovascular Effects of Exercise
- Ion channel regulation and function
- Connective tissue disorders research
- RNA and protein synthesis mechanisms
- Cardiac electrophysiology and arrhythmias
- RNA regulation and disease
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2016-2025
Boston Children's Hospital
2016-2025
Harvard University
2016-2025
Hospital for Sick Children
2017-2024
Boston Children's Museum
2012-2024
University College London
2024
SickKids Foundation
2024
Great Ormond Street Hospital
2024
Broad Institute
2021-2024
Genomics (United Kingdom)
2014-2023
Background —The congenital long-QT syndrome (LQTS) is caused by mutations on several genes, all of which encode cardiac ion channels. The progressive understanding the electrophysiological consequences these opens unforeseen possibilities for genotype-phenotype correlation studies. Preliminary observations suggested that conditions (“triggers”) associated with events may in large part be gene specific. Methods and Results —We identified 670 LQTS patients known genotype (LQT1, n=371; LQT2,...
Transcriptome sequencing improves the diagnostic rate for Mendelian disease in patients whom genetic analysis has not returned a diagnosis.
Genome sequencing is often pivotal in the diagnosis of rare diseases, but many these conditions lack specific treatments. We describe how molecular a rare, fatal neurodegenerative condition led to rational design, testing, and manufacture milasen, splice-modulating antisense oligonucleotide drug tailored particular patient. Proof-of-concept experiments cell lines from patient served as basis for launching an "N-of-1" study milasen within 1 year after first contact with There were no serious...
Timothy syndrome (TS) is a multisystem disorder that causes syncope and sudden death from cardiac arrhythmias. Prominent features include congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, autism. All TS individuals have syndactyly (webbing of fingers toes). We discovered resulted recurrent, de novo L-type calcium channel (Ca V 1.2) mutation, G406R. G406 located in alternatively spliced exon 8A, encoding transmembrane segment S6 domain I. Here,...
Every year, ∼450,000 individuals in the United States die suddenly of cardiac arrhythmia. We identified a variant sodium channel gene SCN5A that is associated with arrhythmia African Americans ( P = 0.000028) and linked risk an African-American family 0.005). In transfected cells, allele (Y1102) accelerated activation, increasing likelihood abnormal repolarization About 13.2% carry Y1102 allele. Because has subtle effect on risk, most carriers will never have However, may be useful molecular...
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...
ContextThe serotonergic (5-hydroxytryptamine [5-HT]) neurons in the medulla oblongata project extensively to autonomic and respiratory nuclei brainstem spinal cord help regulate homeostatic function. Previously, abnormalities 5-HT receptor binding medullae of infants dying from sudden infant death syndrome (SIDS) were identified, suggesting that medullary dysfunction may be responsible for a subset SIDS cases.ObjectiveTo investigate cellular defects associated with altered pathways...
There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into best practices in the areas of sequence data generation, analysis, interpretation reporting. The CLARITY Challenge was designed spur convergence diagnosing genetic disease starting from case history data. DNA samples were obtained three families with heritable disorders genomic donated by platform vendors....
Replacing or editing disease-causing mutations holds great promise for treating many human diseases. Yet, delivering therapeutic genetic modifiers to specific cells in vivo has been challenging, particularly large, anatomically distributed tissues such as skeletal muscle. Here, we establish an strategy evolve and stringently select capsid variants of adeno-associated viruses (AAVs) that enable potent delivery desired tissues. Using this method, identify a class RGD motif-containing capsids...
Diamond-Blackfan anemia (DBA) is a hypoplastic characterized by impaired production of red blood cells, with approximately half all cases attributed to ribosomal protein gene mutations. We performed exome sequencing on two siblings who had no known pathogenic mutations for DBA and identified mutation in the encoding hematopoietic transcription factor GATA1. This mutation, which occurred at splice site GATA1 gene, full-length form protein. further an additional patient carrying distinct same...
Over the past decade there have been major advances in defining genetic basis of majority congenital myopathy subtypes. However relationship between each myopathy, defined on histological grounds, and cause is complex. Many myopathies are due to mutations more than one gene, same gene can different muscle pathologies. The International Standard Care Committee for Congenital Myopathies performed a literature review consulted group experts field develop summary (1) key features common all...