Meghan C. Towne
A5074881951- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- BRCA gene mutations in cancer
- Metabolism and Genetic Disorders
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Genetic Associations and Epidemiology
- Mitochondrial Function and Pathology
- Genetic factors in colorectal cancer
- Ubiquitin and proteasome pathways
- Neurological disorders and treatments
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- Cancer Genomics and Diagnostics
- Cardiac electrophysiology and arrhythmias
- Signaling Pathways in Disease
- Ion Transport and Channel Regulation
- Lipid metabolism and disorders
- Prenatal Screening and Diagnostics
- Aortic aneurysm repair treatments
- Connective tissue disorders research
- Diet and metabolism studies
- CRISPR and Genetic Engineering
- Parathyroid Disorders and Treatments
- Cellular transport and secretion
Ambry Genetics (United States)
2018-2025
Boston University
2023
Boston Children's Hospital
2013-2018
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2013-2018
Harvard University
2013-2018
Center for Discovery
2016-2017
Dana-Farber Cancer Institute
2017
Institut thématique Génétique, génomique et bioinformatique
2013
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....
A critical step in preserving protein homeostasis is the recognition, binding, unfolding, and translocation of substrates by six AAA-ATPase proteasome subunits (ATPase-associated with various cellular activities) termed PSMC1-6, which are required for degradation proteins 26 S proteasomes. Here, we identified 15 de novo missense variants PSMC3 gene encoding subunit PSMC3/Rpt5 23 unrelated heterozygous patients an autosomal dominant form neurodevelopmental delay intellectual disability....
We describe a child with onset of command auditory hallucinations and behavioral regression at 6 yr age in the context longer standing selective mutism, aggression, mild motor delays. His genetic evaluation included chromosomal microarray analysis whole-exome sequencing. Sequencing revealed previously unreported heterozygous de novo mutation c.385G>A ATP1A3, predicted to result p.V129M amino acid change. This gene codes for neuron-specific isoform catalytic α-subunit ATP-dependent...
Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 PRPF19, encoding spliceosome subunits neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo missense (including seven recurrent 30 individuals) six PRPF19 variants. Eight dysregulated model substrate....
Diagnosis of hereditary amyloid transthyretin (hATTR) amyloidosis with cardiomyopathy is frequently delayed, in large part because symptom overlap other cardiovascular diseases and limited provider knowledge this disease. The sponsored referred hATTR Compass Genetic Testing Program (Ionis, Carlsbad, CA; Ambry Genetics, Aliso Viejo, CA) provided no-cost genetic testing to adults a family history or clinical suspicion amyloidosis. This study aims characterize patients increase awareness for hATTR.
Abstract SPOUT1/CENP-32 encodes a putative SPOUT RNA methyltransferase previously identified as mitotic chromosome associated protein. depletion leads to centrosome detachment from the spindle poles and misalignment. Aided by gene matching platforms, here we identify 28 individuals with neurodevelopmental delays 21 families bi-allelic variants in detected exome/genome sequencing. Zebrafish spout1/cenp-32 mutants show reduction larval head size concomitant apoptosis likely altered cell cycle...
We describe a large Lebanese family with two affected members, young female proband and her male cousin, who had multisystem involvement including profound global developmental delay, severe hypotonia weakness, respiratory insufficiency, blindness, lactic acidemia-findings consistent an underlying mitochondrial disorder. Whole-exome sequencing was performed on DNA from the both parents. The cousin carried compound heterozygous mutations in PMPCA gene that encodes for α-mitochondrial...
Cystic fibrosis (CF) remains the most lethal genetic disease in Caucasian population. However, there is great variability clinical phenotypes and survival times, even among patients harboring same genotype. We identified five with CF a homozygous F508del mutation CFTR gene who were their fifth or sixth decade of life had shown minimal changes lung function over longitudinal period more than 20 years. Because rarity this long-term nonprogressive phenotype, we hypothesized these individuals...
The current obesity epidemic is attributed to complex interactions between genetic and environmental factors. However, a limited number of cases, especially those with early-onset severe obesity, are linked single gene defects. Rapid-onset hypothalamic dysfunction, hypoventilation autonomic dysregulation (ROHHAD) one the syndromes that presents abrupt-onset extreme weight gain an unknown basis. To identify underlying etiology in child morbid hypoventilation, behavioral disturbances who was...
<b><i>Background:</i></b> Long-gap esophageal atresia (LGEA) may have clinical and syndromic presentations different from those of (EA) that affects shorter segments the esophagus (non-LGEA). This suggest unique underlying developmental mechanisms. <b><i>Objectives:</i></b> We sought to characterize differences between LGEA non-LGEA by carefully phenotyping a cohort EA patients, furthermore assess molecular genetic findings in subset them....
Purpose Much information on parental perspectives the return of individual research results (IRR) in pediatric genomic is based hypothetical rather than actual IRR. Our aim was to understand how expected utility parents who received IRR their child from a genetic study compared received. Methods We conducted telephone interviews with through participation Manton Center for Orphan Disease Research Gene Discovery Core (GDC) at Boston Children's Hospital (BCH). Results Five themes emerged...
Abstract Patients with dystonia are particularly appropriate for diagnostic exome sequencing (DES), due to the complex, diverse features and genetic heterogeneity. Personal family history data were collected from test requisition forms medical records 189 patients reported available members received clinical DES. Of them, 20.2% had a positive finding associated dystonia. Detection rates cases isolated combined 22.4% 25.0%, respectively. 71.4% of cohort co‐occurring non‐movement‐related...
Copy number variability at 16p13.11 has been associated with intellectual disability, autism, schizophrenia, epilepsy, and attention‐deficit hyperactivity disorder. Adolescent/adult‐ onset psychosis reported in a subset of these cases. Here, we report on two children CNVs that developed before the age 7. The genotype neuropsychiatric abnormalities patients highlight several overlapping genes have possible mechanistic relevance to pathways previously implicated Autism Spectrum Disorders,...