Anne O'Donnell-Luria, MD, PhD
Attending Physician, Division of Genetics and Genomics
Associate Professor of Pediatrics, Harvard Medical School
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Anne O'Donnell-Luria, MD, PhD
Attending Physician, Division of Genetics and Genomics
Associate Professor of Pediatrics, Harvard Medical School
Medical Services
Languages
English
Education
Medical School
Columbia University Medical School
2011
New York
NY
Residency
Medical Genetics
Boston Combined Pediatrics Residency Program (BCRP)
2017
Boston
MA
Fellowship
Boston Children's Hospital
2016
Boston
MA
Certifications
American Board of Medical Genetics and Genomics (Clinical Genetics)
American Board of Medical Genetics and Genomics (Medical Biochemical Genetics)
American Board of Pediatrics (General)
Professional History
Dr. Anne O’Donnell-Luria is the Co-Director of the Broad Institute Center for Mendelian Genomics (CMG), she leads a team analyzing thousands of rare disease families to improve genetic diagnosis and novel disease gene discovery. Her research is focused on using large-scale genomics to understand the mechanisms of incomplete penetrance.
Dr. O’Donnell-Luria co-leads the EpiChroma clinic, A Genetics Clinic for Epigenetic and Chromatin Disorders, [2]http://epichromaclinic.com/. The EpiChroma clinic focuses on diagnosing and caring for children and families with disorders due to mutations in the DNA methylation or histone machinery. By working together with families, she hopes to improve patient management and increase research for these conditions, while educating providers and families about epigenetics and the associated conditions. She also sees patients with inborn errors of metabolism and other rare genetic conditions.
Dr. O’Donnell-Luria is trained in clinical genetics, biochemical genetics and pediatrics. She completed her MD/PhD training at Columbia University Medical School in New York. Her thesis research focused on the role of DNA methylation alterations in complex disease including cancer and neuropsychiatric disease. She became interested in rare disease during medical school, leading her to be the first to complete the Combined Pediatrics-Genetics Residency Training Program at Boston Children’s Hospital and Harvard Medical School. She further completed a Fellowship in Medical Biochemical Genetics at Boston Children’s Hospital.
Publications
Large Class of Neurodevelopmental Disorders Requires Genome Sequencing for Diagnosis. View Abstract
GREGoR: accelerating genomics for rare diseases. View Abstract
Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database. View Abstract
Towards Characterizing the Developmental and Behavioral Profiles of ODLURO Syndrome: Shared Features With Wiedemann-Steiner Syndrome and Kabuki Syndrome. View Abstract
Neuroimaging Findings in Carbonic Anhydrase VA Deficiency: A Case Series Highlighting Diagnostic and Prognostic Patterns in a Potentially Reversible Mitochondrial Dysfunction. View Abstract
Transcriptome-wide outlier approach identifies individuals with minor spliceopathies. View Abstract
Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies. View Abstract
Predicting expression-altering promoter mutations with deep learning. View Abstract
Academic Learning Profiles Across Disorders of KMT2 Gene Family: Superimposed and Distinct Features Across Kabuki, Wiedemann-Steiner and ODLURO Syndromes. View Abstract
Search for a genetic cause of variably protease-sensitive prionopathy. View Abstract
Expectations for papers performing Mendelian randomization analyses. View Abstract
AP2M1 Is a Candidate Gene for Microcephaly and Intellectual Disability in 3q27.1 Deletions. View Abstract
Delineating the Cognitive Profile of ODLURO Syndrome: Emergent Clues on the Endophenotype Across KMT2 Disorders. View Abstract
Missense variants in TUBA4A cause myo-tubulinopathies. View Abstract
HCN2-Associated Neurodevelopmental Disorders: Data from Patients and Xenopus Cell Models. View Abstract
Scalable automated reanalysis of genomic data in research and clinical rare disease cohorts. View Abstract
Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption. View Abstract
HMGCS1 variants cause rigid spine syndrome amenable to mevalonic acid treatment in an animal model. View Abstract
Gene-based calibration of high-throughput functional assays for clinical variant classification. View Abstract
Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases. View Abstract
The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the clinical validity of 111 gene-disease relationships. View Abstract
Monoallelic de novo variants in DDX17 cause a neurodevelopmental disorder. View Abstract
ADAT3 variants disrupt the activity of the ADAT tRNA deaminase complex and impair neuronal migration. View Abstract
Calibration of additional computational tools expands ClinGen recommendation options for variant classification with PP3/BP4 criteria. View Abstract
Gene Identification for Ocular Congenital Cranial Motor Neuron Disorders Using Human Sequencing, Zebrafish Screening, and Protein Binding Microarrays. View Abstract
Male proband with intractable seizures and a de novo start-codon-disrupting variant in GLUL. View Abstract
Evaluating predictors of kinase activity of STK11 variants identified in primary human non-small cell lung cancers. View Abstract
Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection. View Abstract
Detailed tandem repeat allele profiling in 1,027 long-read genomes reveals genome-wide patterns of pathogenicity. View Abstract
Novel Phenotypes and Genotype-Phenotype Correlations in a Large Clinical Cohort of Patients With Kleefstra Syndrome. View Abstract
Diagnosing missed cases of spinal muscular atrophy in genome, exome, and panel sequencing data sets. View Abstract
Functional associations of evolutionarily recent human genes exhibit sensitivity to the 3D genome landscape and disease. View Abstract
Neurodevelopmental disorders associated variants in ADAT3 disrupt the activity of the ADAT2/ADAT3 tRNA deaminase complex and impair neuronal migration. View Abstract
Neurodevelopmental Disorder Caused by Deletion of CHASERR, a lncRNA Gene. View Abstract
Leaving no patient behind! Expert recommendation in the use of innovative technologies for diagnosing rare diseases. View Abstract
Assessment of the evidence yield for the calibrated PP3/BP4 computational recommendations. View Abstract
Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders. View Abstract
Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes. View Abstract
De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome. View Abstract
Evaluating predictors of kinase activity of STK11 variants identified in primary human non-small cell lung cancers. View Abstract
Improving transparency of computational tools for variant effect prediction. View Abstract
Genome Sequencing for Diagnosing Rare Diseases. View Abstract
De novoTLK1 and MDM1 mutations in a patient with a neurodevelopmental disorder and immunodeficiency. View Abstract
The landscape of regional missense mutational intolerance quantified from 125,748 exomes. View Abstract
Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project. View Abstract
Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease. View Abstract
Genome and RNA sequencing boost neuromuscular diagnoses to 62% from 34% with exome sequencing alone. View Abstract
Mono and biallelic variants in HCN2 cause severe neurodevelopmental disorders. View Abstract
Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy. View Abstract
Recurring homozygous ACTN2 variant (p.Arg506Gly) causes a recessive myopathy. View Abstract
Author Correction: A genomic mutational constraint map using variation in 76,156 human genomes. View Abstract
Heterozygous loss-of-function SMC3 variants are associated with variable growth and developmental features. View Abstract
Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort. View Abstract
A gene pathogenicity tool "GenePy" identifies missed biallelic diagnoses in the 100,000 Genomes Project. View Abstract
Author Correction: Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death. View Abstract
A Panel-Agnostic Strategy 'HiPPo' Improves Diagnostic Efficiency in the UK Genomic Medicine Service. View Abstract
Inferring compound heterozygosity from large-scale exome sequencing data. View Abstract
A genomic mutational constraint map using variation in 76,156 human genomes. View Abstract
Exome Sequencing and the Identification of New Genes and Shared Mechanisms in Polymicrogyria. View Abstract
Advanced variant classification framework reduces the false positive rate of predicted loss-of-function variants in population sequencing data. View Abstract
Systematic evaluation of genome sequencing for the diagnostic assessment of autism spectrum disorder and fetal structural anomalies. View Abstract
Beyond the exome: What's next in diagnostic testing for Mendelian conditions. View Abstract
Advancing Understanding of Inequities in Rare Disease Genomics. View Abstract
DNM1L variant presenting as adolescent-onset sensory neuronopathy, spasticity, dystonia, and ataxia. View Abstract
Classical phenylketonuria presenting as maternal PKU syndrome in the offspring of an intellectually normal woman. View Abstract
Phenotype and genetic analysis of data collected within the first year of NeuroDev. View Abstract
Rare penetrant mutations confer severe risk of common diseases. View Abstract
The landscape of tolerated genetic variation in humans and primates. View Abstract
First-Tier Next Generation Sequencing for Newborn Screening: An Important Role for Biochemical Second-Tier Testing. View Abstract
LHX2 haploinsufficiency causes a variable neurodevelopmental disorder. View Abstract
National Human Genome Research Institute Genomic Data Science Analysis, Visualization, and Informatics Lab-Space: Reaching out to Clinicians. View Abstract
Untargeted metabolomics profiling in pediatric patients and adult populations indicates a connection between lipid imbalance and epilepsy. View Abstract
Transcriptome and Genome Analysis Uncovers a DMD Structural Variant: A Case Report. View Abstract
Variants in DTNA cause a mild, dominantly inherited muscular dystrophy. View Abstract
Interpreting variants in genes affected by clonal hematopoiesis in population data. View Abstract
Bi-allelic TTI1 variants cause an autosomal-recessive neurodevelopmental disorder with microcephaly. View Abstract
Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death. View Abstract
Targeting de novo loss-of-function variants in constrained disease genes improves diagnostic rates in the 100,000 Genomes Project. View Abstract
Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3/BP4 criteria. View Abstract
Developmental dynamics of RNA translation in the human brain. View Abstract
Response to Ramos et al. View Abstract
Wide range of phenotypic severity in individuals with late truncations unique to the predominant CDKL5 transcript in the brain. View Abstract
Recommendations for clinical interpretation of variants found in non-coding regions of the genome. View Abstract
Diagnostic capabilities of nanopore long-read sequencing in muscular dystrophy. View Abstract
A gene-to-patient approach uplifts novel disease gene discovery and identifies 18 putative novel disease genes. View Abstract
seqr: A web-based analysis and collaboration tool for rare disease genomics. View Abstract
Genes To Mental Health (G2MH): A Framework to Map the Combined Effects of Rare and Common Variants on Dimensions of Cognition and Psychopathology. View Abstract
Recurrent de novo missense variants across multiple histone H4 genes underlie a neurodevelopmental syndrome. View Abstract
Centers for Mendelian Genomics: A decade of facilitating gene discovery. View Abstract
Recessive variants in COL25A1 gene as novel cause of arthrogryposis multiplex congenita with ocular congenital cranial dysinnervation disorder. View Abstract
Delineation of a novel neurodevelopmental syndrome associated with PAX5 haploinsufficiency. View Abstract
Mendelian etiologies identified with whole exome sequencing in cerebral palsy. View Abstract
Variant interpretation using population databases: Lessons from gnomAD. View Abstract
Lessons learnt from multifaceted diagnostic approaches to the first 150 families in Victoria's Undiagnosed Diseases Program. View Abstract
Novel variants in KAT6B spectrum of disorders expand our knowledge of clinical manifestations and molecular mechanisms. View Abstract
Addendum: The mutational constraint spectrum quantified from variation in 141,456 humans. View Abstract
O'Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum. View Abstract
Unique variants in CLCN3, encoding an endosomal anion/proton exchanger, underlie a spectrum of neurodevelopmental disorders. View Abstract
Strategies to Uplift Novel Mendelian Gene Discovery for Improved Clinical Outcomes. View Abstract
Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes. View Abstract
Familial thrombocytopenia due to a complex structural variant resulting in a WAC-ANKRD26 fusion transcript. View Abstract
A form of muscular dystrophy associated with pathogenic variants in JAG2. View Abstract
Comprehensive analysis of ADA2 genetic variants and estimation of carrier frequency driven by a function-based approach. View Abstract
A form of muscular dystrophy associated with pathogenic variants in JAG2. View Abstract
Novel variants in TUBA1A cause congenital fibrosis of the extraocular muscles with or without malformations of cortical brain development. View Abstract
Author Correction: Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes. View Abstract
Author Correction: Characterising the loss-of-function impact of 5' untranslated region variants in 15,708 individuals. View Abstract
Author Correction: The mutational constraint spectrum quantified from variation in 141,456 humans. View Abstract
Author Correction: Transcript expression-aware annotation improves rare variant interpretation. View Abstract
Author Correction: A structural variation reference for medical and population genetics. View Abstract
De novo TRIM8 variants impair its protein localization to nuclear bodies and cause developmental delay, epilepsy, and focal segmental glomerulosclerosis. View Abstract
Alternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome. View Abstract
Neurogenetic fetal akinesia and arthrogryposis: genetics, expanding genotype-phenotypes and functional genomics. View Abstract
Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes. View Abstract
Characterising the loss-of-function impact of 5' untranslated region variants in 15,708 individuals. View Abstract
A structural variation reference for medical and population genetics. View Abstract
The mutational constraint spectrum quantified from variation in 141,456 humans. View Abstract
Transcript expression-aware annotation improves rare variant interpretation. View Abstract
Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7. View Abstract
Apcdd1 is a dual BMP/Wnt inhibitor in the developing nervous system and skin. View Abstract
Identification of pathogenic variant enriched regions across genes and gene families. View Abstract
Characterization of Prevalence and Health Consequences of Uniparental Disomy in Four Million Individuals from the General Population. View Abstract
Improving the Understanding of Genetic Variants in Rare Disease With Large-scale Reference Populations. View Abstract
Genome Sequencing Identifies the Pathogenic Variant Missed by Prior Testing in an Infant with Marfan Syndrome. View Abstract
Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy. View Abstract
Unique bioinformatic approach and comprehensive reanalysis improve diagnostic yield of clinical exomes. View Abstract
The Genetic Landscape of Diamond-Blackfan Anemia. View Abstract
Insights into genetics, human biology and disease gleaned from family based genomic studies. View Abstract
Using High-Resolution Variant Frequencies Empowers Clinical Genome Interpretation and Enables Investigation of Genetic Architecture. View Abstract
Reply to 'Selective effects of heterozygous protein-truncating variants'. View Abstract
The Genetic Landscape of Diamond-Blackfan Anemia. View Abstract
matchbox: An open-source tool for patient matching via the Matchmaker Exchange. View Abstract
Megaloblastic Anemia Progressing to Severe Thrombotic Microangiopathy in Patients with Disordered Vitamin B12 Metabolism: Case Reports and Literature Review. View Abstract
Utility of rapid whole-exome sequencing in the diagnosis of Niemann-Pick disease type C presenting with fetal hydrops and acute liver failure. View Abstract
ClinVar data parsing. View Abstract
Using high-resolution variant frequencies to empower clinical genome interpretation. View Abstract
Improving genetic diagnosis in Mendelian disease with transcriptome sequencing. View Abstract
Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity. View Abstract
Estimating the selective effects of heterozygous protein-truncating variants from human exome data. View Abstract
Pathogenic ASXL1 somatic variants in reference databases complicate germline variant interpretation for Bohring-Opitz Syndrome. View Abstract
Brain MRS glutamine as a biomarker to guide therapy of hyperammonemic coma. View Abstract
Analysis of protein-coding genetic variation in 60,706 humans. View Abstract
A Clinician's perspective on clinical exome sequencing. View Abstract
Health and population effects of rare gene knockouts in adult humans with related parents. View Abstract
Quantifying prion disease penetrance using large population control cohorts. View Abstract
Mutations in ARID2 are associated with intellectual disabilities. View Abstract
Turner syndrome: update on biology and management across the life span. View Abstract
Methylation Abnormalities in Mammary Carcinoma: The Methylation Suicide Hypothesis. View Abstract
Increased DNA methylation in the suicide brain. View Abstract
Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal behavior and dysregulated gene expression. View Abstract
MethylomeDB: a database of DNA methylation profiles of the brain. View Abstract
Role of CpG context and content in evolutionary signatures of brain DNA methylation. View Abstract
Chromatin and sequence features that define the fine and gross structure of genomic methylation patterns. View Abstract
Mammalian cytosine methylation at a glance. View Abstract
Hyperconserved CpG domains underlie Polycomb-binding sites. View Abstract
Solvent isotope effects on alpha-glucosidase. View Abstract
Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation. View Abstract
KMT2E-Related Neurodevelopmental Disorder View Abstract