Elise Valkanas
A5043451910- Genomics and Rare Diseases
- Muscle Physiology and Disorders
- Genomic variations and chromosomal abnormalities
- Prenatal Screening and Diagnostics
- Ubiquitin and proteasome pathways
- Genetic Neurodegenerative Diseases
- Hereditary Neurological Disorders
- Cardiomyopathy and Myosin Studies
- Retinal Development and Disorders
- Neurogenetic and Muscular Disorders Research
- Biomedical Text Mining and Ontologies
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Lysosomal Storage Disorders Research
- Autopsy Techniques and Outcomes
- Ocular Disorders and Treatments
- Ion channel regulation and function
- dental development and anomalies
- Parvovirus B19 Infection Studies
- Genetics, Bioinformatics, and Biomedical Research
- Medical Coding and Health Information
- Fetal and Pediatric Neurological Disorders
- Axon Guidance and Neuronal Signaling
- Pharmaceutical studies and practices
- Adipose Tissue and Metabolism
Massachusetts General Hospital
2016-2024
Broad Institute
2017-2024
Broad Center
2024
Harvard University
2016-2024
Massachusetts Institute of Technology
2018-2021
Children's Hospital at Westmead
2021
Boston University
2019
Office of the Director
2015-2017
National Institutes of Health
2015-2017
National Human Genome Research Institute
2015-2016
Structural variants (SVs) rearrange large segments of DNA
Medical diagnosis and molecular or biochemical confirmation typically rely on the knowledge of clinician. Although this is very difficult in extremely rare diseases, we hypothesized that recording patient phenotypes Human Phenotype Ontology (HPO) terms computationally ranking putative disease-associated sequence variants improves diagnosis, particularly for patients with atypical clinical profiles.
Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and heterogeneity means that a diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups disease patients better understand etiology.Exome sequencing was applied 1001 undiagnosed recruited from more than 40 neuromuscular referral centers; standardized phenotypic information collected for each patient. Exomes were examined variants in 429 genes associated...
Abstract Pregnancy loss and perinatal death are devastating events for families. We assessed ‘genomic autopsy’ as an adjunct to standard autopsy 200 families who had experienced fetal or newborn death, providing a definitive candidate genetic diagnosis in 105 Our cohort provides evidence of severe atypical utero presentations known disorders identifies novel phenotypes disease genes. Inheritance 42% diagnoses were either autosomal recessive (30.8%), X-linked (3.8%) dominant (excluding de...
SUMMARY Structural variants (SVs) rearrange large segments of the genome and can have profound consequences for evolution human diseases. As national biobanks, disease association studies, clinical genetic testing grow increasingly reliant on sequencing, population references such as Genome Aggregation Database (gnomAD) become integral interpreting variation. To date, no large-scale reference maps SVs exist from high-coverage sequencing comparable to those available point mutations in...
Dystroglycanopathies are a clinically and genetically heterogeneous group of disorders that typically characterised by limb-girdle muscle weakness. Mutations in 18 different genes have been associated with dystroglycanopathies, the encoded proteins which modulate binding α-dystroglycan to extracellular matrix ligands altering its glycosylation. This results disruption structural integrity myocyte, ultimately leading degeneration. Deep phenotypic information was gathered using PhenoTips...
To investigate the effect of PLXNA1 variants on phenotype patients with autosomal dominant and recessive inheritance patterns to functionally characterize zebrafish homologs plxna1a plxna1b during development.We assembled ten from seven families biallelic or de novo variants. We describe genotype-phenotype correlations, investigated by structural modeling, used Morpholino knockdown experiments in embryonic role plxna1b.Shared phenotypic features among include global developmental delay...
Abstract Objective Most families with heritable neuromuscular disorders do not receive a molecular diagnosis. Here we evaluate diagnostic utility of exome, genome, RNA sequencing, and protein studies provide evidence‐based recommendations for their integration into practice. Methods In total, 247 suspected monogenic who remained without genetic diagnosis after standard investigations underwent research‐led massively parallel sequencing: disorder gene panel, and/or sequencing to identify...
Traditionally, the use of genomic information for personalized medical decisions relies on prior discovery and validation genotype-phenotype associations. This approach constrains care patients presenting with undescribed problems. The National Institutes Health (NIH) Undiagnosed Diseases Program (UDP) hypothesized that defining disease as maladaptation to an ecological niche allows delineation a logical framework diagnose evaluate such patients. Herein, we present philosophical bases,...
Rare disease investigators constantly face challenges in identifying additional cases to build evidence for gene-disease causality. The Matchmaker Exchange (MME) addresses this limitation by providing a mechanism matching patients across genomic centers via federated network. MME has revolutionized searching making it possible query institutional boundaries, so that what was once laborious and manual process of contacting researchers is now automated computable. However, while the network...
Next-generation sequencing is commonly used to screen for pathogenic mutations in families with Mendelian disorders, but due the pace of discoveries, gaps have widened some diseases between genetic and pathophysiological knowledge. We recruited analyzed 16 limb-girdle muscular dystrophy (LGMD) Arab descent from Saudi Arabia Sudan who did not confirmed diagnoses. The analysis included both traditional next-generation approaches. Cellular metabolic studies were performed on Pyroxd1 siRNA C2C12...
Failure to thrive arises as a complication of heterogeneous group disorders. We describe two female siblings with spastic paraplegia and global developmental delay but also, atypically for the HSPs, poor weight gain classified failure thrive. After extensive clinical biochemical investigations failed identify etiology, we used exome sequencing biallelic UNC80 mutations (NM_032504.1:c.[3983‐3_3994delinsA];[2431C>T]. The paternally inherited NM_032504.1:c.3983‐3_3994delinsA is predicted...
ABSTRACT Current clinical guidelines recommend three genetic tests for the assessment of fetal structural anomalies: karyotype to detect microscopically-visible balanced and unbalanced chromosomal rearrangements, microarray (CMA) sub-microscopic copy number variants (CNVs), exome sequencing (ES) identify individual nucleotide changes in coding sequence. Advances genome (GS) analysis suggest that it is poised displace sequential application all conventional become a single diagnostic approach...
Abstract Purpose With the advent of gene therapies for inherited retinal degenerations (IRDs), genetic diagnostics will have an increasing role in clinical decision-making. Yet cause disease cannot be identified using exon-based sequencing a significant portion patients. We hypothesized that non-coding mutations contribute significantly to causality IRDs and evaluated patients with single coding RPGRIP1 test this hypothesis. Methods IRD families underwent targeted panel sequencing. Unsolved...