ABOUT THE RESEARCHER

OVERVIEW

Dr. Brownstein specializes in the discovery of new genes for rare and orphan diseases. She has put her background and training to use in projects with the Manton Center for Orphan Disease Research, the Developmental Neuropsychiatry Program, The Tommy Fuss Center, and Robert’s Program in Sudden and Unexpected Death in Pediatrics. Her research has elucidated phosphate regulation and the genetic causes of intellectual disability.

Laboratory Projects:

  1. Juvenile Psychosis
  2. Dr. Brownstein is working in conjunction with the Developmental Neuropsychiatry Program to elucidate the genetic causes of psychosis in very young children.
  3. Orphan and Rare Diseases
  4. In conjunction in the Manton Center, Dr. Brownstein works on all areas of rare disease and has a particular interest in chronic pain and pain insensitivity disorders.
  5. VivilyThis unique initiative assesses real-time availability for functional experiments, allowing laboratories to maximize productivity and clinician scientists to minimize time and cost. Vivily aims to enable follow-up experiments on every patient VUS. Vivily is a partnership between GETTYLAB, the Innovation and Digital Health Accelerator, and the Molecular Genomics Core Facility.

BACKGROUND

Dr. Brownstein is an Assistant Professor of Pediatrics at Harvard Medical School, a Research Associate in Genetics and Genomics at Boston Children’s Hospital, and the Assistant Director of the Molecular Genomics Core Facility. Dr. Brownstein has over 10 years of experience in genetics and toxicology, specializing in gene discovery. Before joining BCH in 2011 Dr. Brownstein worked as a toxicologist for the Massachusetts Department of Public Health, and at various startups in Health 2.0.

Selected Publications

  1. Brownstein CA, Towne MC, Luquette LJ, Harris DJ, Marinakis NS, et al. Mutation of KCNJ8 in a patient with Cantú syndrome with unique vascular abnormalities - support for the role of K(ATP) channels in this condition. Eur J Med Genet. 2013 Dec;56(12):678-82. PMCID: PMC3902017
  2. Brownstein CA, Beggs AH, Homer N, Merriman B, Yu TW, et al. An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge. Genome Biol. 2014 Mar 25;15(3):R53. PMCID: PMC4073084
  3. Smedemark-Margulies N, Brownstein CA, Vargas S, Tembulkar SK, Towne MC, et al. A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia. Cold Spring Harb Mol Case Stud. 2016 Sep;2(5).
  4. Brownstein CA, Beggs AH, Rodan L, et al. Clinical heterogeneity associated with KCNA1 mutations include cataplexy and nonataxic presentations. Neurogenetics. 2015 Sep 22. PMID: 26395884
  5. Brownstein CA, Kleiman RJ, Engle EC, Towne MC, D'Angelo EJ, et al. Overlapping 16p13.11 deletion and gain of copies variations associated with childhood onset psychosis include genes with mechanistic implications for autism associated pathways: Two case reports. Am J Med Genet A. 2016 May;170A(5):1165-73.

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. A homozygous stop-gain variant in ARHGAP42 is associated with childhood interstitial lung disease, systemic hypertension, and immunological findings. PLoS Genet. 2021 Jul; 17(7):e1009639. View abstract
  2. Early role for a Na+,K+-ATPase (ATP1A3) in brain development. Proc Natl Acad Sci U S A. 2021 Jun 22; 118(25). View abstract
  3. A data-driven architecture using natural language processing to improve phenotyping efficiency and accelerate genetic diagnoses of rare disorders. HGG Adv. 2021 Jul; 2(3). View abstract
  4. Underrepresentation of Phenotypic Variability of 16p13.11 Microduplication Syndrome Assessed With an Online Self-Phenotyping Tool (Phenotypr): Cohort Study. J Med Internet Res. 2021 03 16; 23(3):e21023. View abstract
  5. RCL1 copy number variants are associated with a range of neuropsychiatric phenotypes. Mol Psychiatry. 2021 05; 26(5):1706-1718. View abstract
  6. Alternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome. Am J Med Genet A. 2021 01; 185(1):119-133. View abstract
  7. Current knowledge of SLC6A1-related neurodevelopmental disorders. Brain Commun. 2020; 2(2):fcaa170. View abstract
  8. A de novo BRPF1 variant in a case of Sudden Unexplained Death in Childhood. Eur J Med Genet. 2020 Sep; 63(9):104002. View abstract
  9. Children's rare disease cohorts: an integrative research and clinical genomics initiative. NPJ Genom Med. 2020; 5:29. View abstract
  10. Children's rare disease cohorts: an integrative research and clinical genomics initiative. NPJ Genom Med. 2020 Jul 06; 5(1):29. View abstract
  11. The role of sodium channels in sudden unexpected death in pediatrics. Mol Genet Genomic Med. 2020 08; 8(8):e1309. View abstract
  12. Congenital Heart Defects Due to TAF1 Missense Variants. Circ Genom Precis Med. 2020 06; 13(3):e002843. View abstract
  13. A novel missense mutation in TFAP2B associated with Char syndrome and central diabetes insipidus. . 2019 07; 179(7):1299-1303. View abstract
  14. Unique bioinformatic approach and comprehensive reanalysis improve diagnostic yield of clinical exomes. Eur J Hum Genet. 2019 09; 27(9):1398-1405. View abstract
  15. ClinPhen extracts and prioritizes patient phenotypes directly from medical records to expedite genetic disease diagnosis. Genet Med. 2019 07; 21(7):1585-1593. View abstract
  16. De novo variant of TRRAP in a patient with very early onset psychosis in the context of non-verbal learning disability and obsessive-compulsive disorder: a case report. BMC Med Genet. 2018 11 13; 19(1):197. View abstract
  17. De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy. . 2018 12; 176(12):2623-2629. View abstract
  18. De novo ATP1A3 and compound heterozygous NLRP3 mutations in a child with autism spectrum disorder, episodic fatigue and somnolence, and muckle-wells syndrome. Mol Genet Metab Rep. 2018 Sep; 16:23-29. View abstract
  19. Plain-language medical vocabulary for precision diagnosis. Nat Genet. 2018 04; 50(4):474-476. View abstract
  20. SCN1A variants associated with sudden infant death syndrome. Epilepsia. 2018 04; 59(4):e56-e62. View abstract
  21. De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability. Am J Hum Genet. 2017 Nov 02; 101(5):768-788. View abstract
  22. Monogenic Hashimoto thyroiditis associated with a variant in the thyroglobulin (TG) gene. J Autoimmun. 2018 01; 86:116-119. View abstract
  23. Homozygous EEF1A2 mutation causes dilated cardiomyopathy, failure to thrive, global developmental delay, epilepsy and early death. Hum Mol Genet. 2017 09 15; 26(18):3545-3552. View abstract
  24. Beta-Ketothiolase Deficiency Presenting with Metabolic Stroke After a Normal Newborn Screen in Two Individuals. JIMD Rep. 2018; 39:45-54. View abstract
  25. AIFM1 mutation presenting with fatal encephalomyopathy and mitochondrial disease in an infant. Cold Spring Harb Mol Case Stud. 2017 03; 3(2):a001560. View abstract
  26. Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy. Muscle Nerve. 2017 05; 55(5):761-765. View abstract
  27. The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD in the United States. J Hum Genet. 2017 Feb; 62(2):243-252. View abstract
  28. Hippocampal Formation Maldevelopment and Sudden Unexpected Death across the Pediatric Age Spectrum. J Neuropathol Exp Neurol. 2016 Oct; 75(10):981-997. View abstract
  29. A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia. Cold Spring Harb Mol Case Stud. 2016 Sep; 2(5):a001008. View abstract
  30. SLC6A1 Mutation and Ketogenic Diet in Epilepsy With Myoclonic-Atonic Seizures. Pediatr Neurol. 2016 11; 64:77-79. View abstract
  31. Creating a scalable clinical pharmacogenomics service with automated interpretation and medical record result integration - experience from a pediatric tertiary care facility. J Am Med Inform Assoc. 2017 01; 24(1):74-80. View abstract
  32. Overlapping 16p13.11 deletion and gain of copies variations associated with childhood onset psychosis include genes with mechanistic implications for autism associated pathways: Two case reports. . 2016 May; 170A(5):1165-73. View abstract
  33. The Matchmaker Exchange: a platform for rare disease gene discovery. Hum Mutat. 2015 Oct; 36(10):915-21. View abstract
  34. Clinical heterogeneity associated with KCNA1 mutations include cataplexy and nonataxic presentations. Neurogenetics. 2016 Jan; 17(1):11-6. View abstract
  35. Data sharing in the undiagnosed diseases network. Hum Mutat. 2015 Oct; 36(10):985-8. View abstract
  36. Clinical management of patients with ASXL1 mutations and Bohring-Opitz syndrome, emphasizing the need for Wilms tumor surveillance. . 2015 Sep; 167A(9):2122-31. View abstract
  37. Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome. J Clin Endocrinol Metab. 2015 May; 100(5):1723-30. View abstract
  38. Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy. J Clin Invest. 2015 Jan; 125(1):456-7. View abstract
  39. Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy. J Clin Invest. 2014 Nov; 124(11):4693-708. View abstract
  40. An assessment of clinician and researcher needs for support in the era of genomic medicine. Per Med. 2014 Aug; 11(6):569-579. View abstract
  41. An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge. Genome Biol. 2014 Mar 25; 15(3):R53. View abstract
  42. Misinterpretation of TPMT by a DTC genetic testing company. Clin Pharmacol Ther. 2014 Jun; 95(6):598-600. View abstract
  43. Identification of KLHL41 Mutations Implicates BTB-Kelch-Mediated Ubiquitination as an Alternate Pathway to Myofibrillar Disruption in Nemaline Myopathy. Am J Hum Genet. 2013 Dec 05; 93(6):1108-17. View abstract
  44. Mutation of KCNJ8 in a patient with Cantú syndrome with unique vascular abnormalities - support for the role of K(ATP) channels in this condition. Eur J Med Genet. 2013 Dec; 56(12):678-82. View abstract
  45. Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy. Am J Hum Genet. 2013 Jul 11; 93(1):6-18. View abstract
  46. Development of a scalable pharmacogenomic clinical decision support service. AMIA Jt Summits Transl Sci Proc. 2013; 2013:60. View abstract
  47. Perceived benefits of sharing health data between people with epilepsy on an online platform. Epilepsy Behav. 2012 Jan; 23(1):16-23. View abstract
  48. Potential for electronic health records and online social networking to redefine medical research. Clin Chem. 2011 Feb; 57(2):196-204. View abstract
  49. The potential research impact of patient reported outcomes on osteogenesis imperfecta. Clin Orthop Relat Res. 2010 Oct; 468(10):2581-5. View abstract
  50. Concordance between site of onset and limb dominance in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2011 Aug; 82(8):853-4. View abstract
  51. Sharing health data for better outcomes on PatientsLikeMe. J Med Internet Res. 2010 Jun 14; 12(2):e19. View abstract
  52. Increased bone volume and correction of HYP mouse hypophosphatemia in the Klotho/HYP mouse. Endocrinology. 2010 Feb; 151(2):492-501. View abstract
  53. The power of social networking in medicine. Nat Biotechnol. 2009 Oct; 27(10):888-90. View abstract
  54. A translocation causing increased alpha-klotho level results in hypophosphatemic rickets and hyperparathyroidism. Proc Natl Acad Sci U S A. 2008 Mar 04; 105(9):3455-60. View abstract
  55. Estimating excess mortality in post-invasion Iraq. N Engl J Med. 2008 Jan 31; 358(5):445-7. View abstract