Casie A. Genetti
A5091462883- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- RNA modifications and cancer
- Congenital heart defects research
- Prenatal Screening and Diagnostics
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Cellular transport and secretion
- RNA Research and Splicing
- BRCA gene mutations in cancer
- Neurogenetic and Muscular Disorders Research
- Metabolism and Genetic Disorders
- Genetic Syndromes and Imprinting
- Neonatal Respiratory Health Research
- Biomedical Text Mining and Ontologies
- Microtubule and mitosis dynamics
- Immunodeficiency and Autoimmune Disorders
- RNA regulation and disease
- Neuroscience of respiration and sleep
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Nuclear Structure and Function
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2016-2024
Boston Children's Hospital
2016-2024
Boston Children's Museum
2023-2024
Harvard University
2016-2024
Genomics (United Kingdom)
2023
Mount Sinai Hospital
2021
Children's Hospital of Philadelphia
2021
Hospital for Sick Children
2021
Driscoll Children's Hospital
2021
Texas A&M University – Corpus Christi
2021
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...
Genetic variants that cause rare disorders may remain elusive even after expansive testing, such as exome sequencing. The diagnostic yield of genome sequencing, particularly a negative evaluation, remains poorly defined.
Abstract Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily protein-coding genes 1 . Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify RNA RNU4-2 as a syndromic NDD gene. encodes U4 small nuclear (snRNA), which is critical component U4/U6.U5 tri-snRNP complex major spliceosome 2 We an 18 base pair region mapping two structural elements...
The greatest opportunity for lifelong impact of genomic sequencing is during the newborn period. "BabySeq Project" a randomized trial that explores medical, behavioral, and economic impacts integrating into care healthy sick newborns.Families newborns are enrolled from Boston Children's Hospital Brigham Women's nurseries, half to receive report includes monogenic disease variants, recessive carrier variants childhood onset or actionable disorders, pharmacogenomic variants. All families...
Objective Comprehensive clinical characterization of congenital titinopathy to facilitate diagnosis and management this important emerging disorder. Methods Using massively parallel sequencing we identified 30 patients from 27 families with 2 pathogenic nonsense, frameshift and/or splice site TTN mutations in trans . We then undertook a detailed analysis the clinical, histopathological imaging features these patients. Results All had prenatal or early onset hypotonia contractures. None...
The transcription factor BCL11B is essential for development of the nervous and immune system, Bcl11b deficiency results in structural brain defects, reduced learning capacity, impaired cell mice. However, precise role humans largely unexplored, except a single patient with missense mutation, affected by multisystem anomalies profound deficiency. Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations BCL11B. Notably, all them are global...
Clinical interpretation of genetic variants in the context patient's phenotype is becoming largest component cost and time expenditure for genome-based diagnosis rare diseases. Artificial intelligence (AI) holds promise to greatly simplify speed genome by integrating predictive methods with growing knowledge disease. Here we assess diagnostic performance Fabric GEM, a new, AI-based, clinical decision support tool expediting interpretation.We benchmarked GEM retrospective cohort 119 probands,...
Introduction: With increasing utility and decreasing cost of genomic sequencing, augmentation standard newborn screening (NBS) programs with sequencing (nGS) has been proposed. Before nGS can be integrated into screening, parents’ perspectives must better understood. Objective: Using data from surveys administered to parents healthy newborns who were enrolled in the BabySeq Project, a randomized clinical trial alongside NBS, this paper reports attitudes regarding population-based NBS...
Abstract In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of inheritance have been described the neuromuscular disease field. Here we show that predicted deleterious SRPK3 , encoding X-linked serine/argenine protein kinase 3, lead a progressive early onset skeletal muscle myopathy only when combination with heterozygous TTN gene. The co-occurrence / was not seen among 76,702 healthy male individuals, and statistical...
<h3>Importance</h3> Newborn genomic sequencing (nGS) may provide health benefits throughout the life span, but there are concerns that it could also have an unfavorable (ie, negative) psychosocial effect on families. <h3>Objective</h3> To assess of nGS families from BabySeq Project, a randomized clinical trial evaluating care newborns well-baby nurseries and intensive units. <h3>Design, Setting, Participants</h3> In this conducted May 14, 2015, to 21, 2019, at units 3 Boston, Massachusetts,...