A5091565411- Genomics and Rare Diseases
- Microtubule and mitosis dynamics
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Sexual Differentiation and Disorders
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Peptidase Inhibition and Analysis
- PI3K/AKT/mTOR signaling in cancer
- Reproductive Health and Technologies
- Glycosylation and Glycoproteins Research
- Cardiac Structural Anomalies and Repair
- Cancer Genomics and Diagnostics
- Protein Tyrosine Phosphatases
- Neurogenetic and Muscular Disorders Research
- Infant Nutrition and Health
- Cerebral Palsy and Movement Disorders
- Lipid metabolism and disorders
- Carbohydrate Chemistry and Synthesis
- Metabolism and Genetic Disorders
- Genetics, Bioinformatics, and Biomedical Research
- Biomedical Text Mining and Ontologies
- Adrenal and Paraganglionic Tumors
- Neurogenesis and neuroplasticity mechanisms
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Boston Children's Hospital
2019-2024
Harvard University
2019-2022
Howard Hughes Medical Institute
2019-2022
Broad Institute
2022
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2022
Boston Children's Museum
2022
Center for Pain and the Brain
2022
Abstract There are thousands of distinct disease entities and concepts, each which known by different sometimes contradictory names. The lack a unified system for managing these poses major challenge both machines humans that need to harmonize information better predict causes treatments disease. Mondo Disease Ontology is an open, community-driven ontology integrates key medical biomedical terminologies, supporting data integration improve diagnosis, treatment, translational research....
Abstract Objectives Cerebral palsy (CP) is the most common childhood motor disability, yet its link to single‐gene disorders under‐characterized. To explore genetic landscape of CP, we conducted whole exome sequencing (WES) in a cohort patients with CP. Methods We performed comprehensive phenotyping and WES on prospective individuals cryptogenic CP (who meet criteria for CP; have no risk factors), non‐cryptogenic at least one factor), masqueraders could be diagnosed but...
Polymicrogyria is the most commonly diagnosed cortical malformation and associated with neurodevelopmental sequelae including epilepsy, motor abnormalities, cognitive deficits. frequently co-occurs other brain malformations or as part of syndromic diseases. Past studies polymicrogyria have defined heterogeneous genetic nongenetic causes but explained only a small fraction cases.
PurposePathogenic variants in genes involved the epigenetic machinery are an emerging cause of neurodevelopment disorders (NDDs). Lysine-demethylase 2B (KDM2B) encodes regulator and mouse models suggest important role during development. We set out to determine whether KDM2B associated with NDD.MethodsThrough international collaborations, we collected data on individuals heterozygous variants. applied methylation arrays peripheral blood DNA samples a signature.ResultsWe recruited total 27...
Abstract The human cerebral cortex is composed of six layers and dozens areas that are molecularly structurally distinct 1–4 . Although single-cell transcriptomic studies have advanced the molecular characterization cortical development, a substantial gap exists owing to loss spatial context during cell dissociation 5–8 Here we used multiplexed error-robust fluorescence in situ hybridization (MERFISH) 9 , augmented with deep-learning-based nucleus segmentation, examine molecular, cellular...
Congenital structural brain malformations have been described in patients with pathogenic phosphatase and tensin homologue (PTEN) variants, but the frequency of cortical PTEN variants their impact on clinical phenotype are not well understood. Our goal was to systematically characterize assess relevance presentation.We searched a local radiology database for who had available magnetic resonance imaging (MRI). The MRI scans were reviewed abnormalities. We electroencephalogram (EEG) data...
Kinesins are canonical molecular motors but can also function as modulators of intracellular signaling. KIF26A, an unconventional kinesin that lacks motor activity, inhibits growth-factor-receptor-bound protein 2 (GRB2)- and focal adhesion kinase (FAK)-dependent signal transduction, its functions in the brain have not been characterized. We report a patient cohort with biallelic loss-of-function variants exhibiting spectrum congenital malformations. In developing brain, KIF26A is...
NUSAP1 encodes a cell cycle-dependent protein with key roles in mitotic progression, spindle formation, and microtubule stability. Both over- under-expression of lead to dysregulation mitosis impaired proliferation. Through exome sequencing Matchmaker Exchange, we identified two unrelated individuals the same recurrent, de novo heterozygous variant (NM_016359.5 c.1209C > A; p.(Tyr403Ter)) NUSAP1. had microcephaly, severe developmental delay, brain abnormalities, seizures. The gene is...
Free oligosaccharides (fOSs) are soluble oligosaccharide species generated during N-glycosylation of proteins. Although little is known about fOS metabolism, the recent identification NGLY1 deficiency, a congenital disorder deglycosylation (CDDG) caused by loss function an enzyme involved in has elicited increased interest processing. The catabolism fOSs been linked to activity specific cytosolic mannosidase, MAN2C1, which cleaves α1,2-, α1,3-, and α1,6-mannose residues. In this study, we...
Polymicrogyria (PMG) is one of the more common malformations human cortical development and often classified by its radiographic pattern distribution. Unilateral polymicrogyria a subtype affecting only portion or all hemisphere. Most currently known genetic etiologies PMG result in bilateral distribution but rarely do they explain unilateral PMG. While overall diagnostic yield testing for 20-30%, has never been assessed independently to determine this unique population.
Introduction: FilaminA ( FLNA ), an X-linked gene encoding actin binding protein, is one of the only known causative genes for periventricular nodular heterotopia (PVNH) and mitral valve (MV) prolapse. mutations have been well associated with familial MV prolapse polyvalvular disease in adults. There limited data, however, on type distribution children mutations. We aim to assess frequency a predominantly pediatric cohort. Methods: retrospectively enrolled subjects from large registry at...