Research Overview

Dr. Miller’s patient care focus is on Neurofibromatosis, a genetic condition causing predisposition to developing nervous system tumors. He is the Director of the Multidisciplinary Neurofibromatosis Program at Boston Children’s Hospital, and the Director of an International NF1 Initiative to apply genomic sequencing technologies to better understand the most aggressive NF1-related tumors with the goal of leading to improved treatments. Dr. Miller is also a leader in several national efforts around best practices for clinical genetics and genetic testing, particularly for pediatric neurodevelopmental disorders. He is Chair of the ACMG Professional Practice and Guidelines Committee and is leading a national effort to update clinical practice guidelines for children with Neurofibromatosis Type 1. He Co-Chairs the ACMG Working Group on Secondary Findings Maintenance related to clinical exome sequencing which published an update to the ACMG list in November, 2016. Dr. Miller is also the Chairperson for the Clinical Phenotyping Working Group for ClinGen, an NHGRI-funded effort to build a clinical genomic database for genotype and phenotype information to improve interpretation of genetic test results. Within ClinGen, he is leading efforts to develop MOC credit for ClinGen database curation work, and to improve the uniformity of condition names related to the entries in ClinGen. He is also a Genetics Editor on the Editorial Board for Epilepsia.

Laboratory Projects

Dr. Miller is engaged in collaborative projects related to genetic testing of tumor samples removed from patients with Neurofibromatosis. This work includes exome- and genome-based sequencing of atypical neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs).

 

Research Background

Dr. Miller received his M.D. and Ph.D. degrees from Washington University School of Medicine in St. Louis, completed a residency in Pediatrics at Yale-New Haven Hospital, and residency/fellowship in medical genetics and clinical molecular genetics at Harvard Medical School. He is board-certified in Clinical Genetics and Clinical Molecular Genetics. In addition to being a practicing Medical Geneticist, Dr. Miller has served Boston Children’s Hospital as Assistant Director of the Genetic Diagnostic Laboratory (GDL) for several years, and is now Medical Director at Claritas Genomics (a subsidiary of Boston Children’s Hospital). Dr. Miller is an Associate Professor of Pediatrics at Harvard Medical School, and an active contributor to the Human Genetics course at the Medical School. Dr. Miller’s experience as a clinician who orders genetic tests and provides results directly to patients, combined with expertise in developing and performing clinical laboratory diagnostic assays, provides him with a unique and valuable perspective at the interface of genomic technology and clinical care.

Selected Publications

  1. Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, Herman GE, Hufnagel SB, Klein TE, Korf BR, McKelvey KD, Ormond KE, Richards CS, Vlangos CN, Watson M, Martin CL, Miller DT (2016). Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2016 Nov 17 [Epub ahead of print].
  2. Olson H, Shen Y, Avallone J, et al. (2014). Copy number variation plays an important role in clinical epilepsy. Ann Neurol 75(6):943-58.
  3. Riggs ER, Wain KE, Riethmaier D, Smith-Packard B, Faucett WA, Hoppman N, Thorland EC, Patel VC, Miller DT (2013). Chromosomal Microarray Impacts Clinical Management. Clinical Genetics. 85(2):147-53.
  4. Coulter ME*, Miller DT*, Harris DJ, Hawley P, Sobeih MMS, Irons M (2011). Chromosomal Microarray Testing Influences Medical Management. Genetics in Medicine 13(9): 770-6.
  5. Miller DT, Adam MP, Aradhya S, et al (2010). Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 86(5):749-64.

Education

Undergraduate School

University of Kentucky
1991 Lexington KY

Medical School

Washington University in St. Louis
1999 St. Louis MO

Residency

Pediatrics Yale New Haven Hospital
2002 New Haven CT

Fellowship

Medical Genetics Harvard Genetics Training Program
2005 Boston MA

Publications

  1. Consideration of disease penetrance in the selection of secondary findings gene-disease pairs: A policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2024 Jul; 26(7):101142. View Abstract
  2. ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2023 08; 25(8):100866. View Abstract
  3. Genomic Patterns of Malignant Peripheral Nerve Sheath Tumor (MPNST) Evolution Correlate with Clinical Outcome and Are Detectable in Cell-Free DNA. Cancer Discov. 2023 03 01; 13(3):654-671. View Abstract
  4. Mosaicism in Tumor Suppressor Gene Syndromes: Prevalence, Diagnostic Strategies, and Transmission Risk. Annu Rev Genomics Hum Genet. 2022 08 31; 23:331-361. View Abstract
  5. The ClinGen Brain Malformation Variant Curation Expert Panel: Rules for somatic variants in AKT3, MTOR, PIK3CA, and PIK3R2. Genet Med. 2022 11; 24(11):2240-2248. View Abstract
  6. ACMG SF v3.1 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2022 07; 24(7):1407-1414. View Abstract
  7. Clinical validity assessment of genes frequently tested on intellectual disability/autism sequencing panels. Genet Med. 2022 09; 24(9):1899-1908. View Abstract
  8. Response to McGurk et al. Genet Med. 2022 03; 24(3):747-748. View Abstract
  9. Correction to: ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021 Aug; 23(8):1582-1584. View Abstract
  10. Chromosomal microarray analysis, including constitutional and neoplastic disease applications, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021 10; 23(10):1818-1829. View Abstract
  11. ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021 08; 23(8):1381-1390. View Abstract
  12. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021 08; 23(8):1391-1398. View Abstract
  13. Clinical Syndromic Phenotypes and the Potential Role of Genetics in Pulmonary Vein Stenosis. Children (Basel). 2021 Feb 10; 8(2). View Abstract
  14. Growth, development, and phenotypic spectrum of individuals with deletions of 2q33.1 involving SATB2. Clin Genet. 2021 04; 99(4):547-557. View Abstract
  15. Correction: Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genet Med. 2020 Oct; 22(10):1731-1732. View Abstract
  16. Insufficient Evidence for "Autism-Specific" Genes. Am J Hum Genet. 2020 05 07; 106(5):587-595. View Abstract
  17. Points to consider for reporting of germline variation in patients undergoing tumor testing: a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2020 07; 22(7):1142-1148. View Abstract
  18. Genomics of MPNST (GeM) Consortium: Rationale and Study Design for Multi-Omic Characterization of NF1-Associated and Sporadic MPNSTs. Genes (Basel). 2020 04 02; 11(4). View Abstract
  19. Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability. Genet Med. 2020 06; 22(6):986-1004. View Abstract
  20. Genetics of human malignant peripheral nerve sheath tumors. Neurooncol Adv. 2020 Jul; 2(Suppl 1):i50-i61. View Abstract
  21. Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genet Med. 2019 11; 21(11):2413-2421. View Abstract
  22. Health Supervision for Children With Neurofibromatosis Type 1. Pediatrics. 2019 05; 143(5). View Abstract
  23. Response to Knoppers et al. Genet Med. 2019 10; 21(10):2403. View Abstract
  24. Correction: Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype-phenotype correlation. Genet Med. 2019 03; 21(3):764-765. View Abstract
  25. Patient re-contact after revision of genomic test results: points to consider-a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2019 04; 21(4):769-771. View Abstract
  26. Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype-phenotype correlation. Genet Med. 2019 04; 21(4):867-876. View Abstract
  27. Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2018 10; 20(10):1105-1113. View Abstract
  28. Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844-848. Am J Hum Genet. 2018 01 04; 102(1):69-87. View Abstract
  29. School liaison program supporting children with neurofibromatosis type 1: a model of care for children with chronic disease. Genet Med. 2018 07; 20(7):785-788. View Abstract
  30. Response to Biesecker. Genet Med. 2017 05; 19(5):605. View Abstract
  31. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2017 02; 19(2):249-255. View Abstract
  32. Long-Gap Esophageal Atresia Is a Unique Entity within the Esophageal Atresia Defect Spectrum. Neonatology. 2017; 111(2):140-144. View Abstract
  33. Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome. Circulation. 2016 Jul 12; 134(2):114-25. View Abstract
  34. A Clinician's perspective on clinical exome sequencing. Hum Genet. 2016 06; 135(6):643-54. View Abstract
  35. Classifying Germline Sequence Variants in the Era of Next-Generation Sequencing. Clin Chem. 2016 06; 62(6):799-806. View Abstract
  36. A Case of HDR Syndrome and Ichthyosis: Dual Diagnosis by Whole-Genome Sequencing of Novel Mutations in GATA3 and STS Genes. J Clin Endocrinol Metab. 2016 Mar; 101(3):837-40. View Abstract
  37. GenomeConnect: matchmaking between patients, clinical laboratories, and researchers to improve genomic knowledge. Hum Mutat. 2015 Oct; 36(10):974-8. View Abstract
  38. Chromosome microarray testing for patients with congenital heart defects reveals novel disease causing loci and high diagnostic yield. BMC Genomics. 2014 Dec 17; 15:1127. View Abstract
  39. Advances in Genetic Discovery and Implications for Counseling of Patients and Families with Autism Spectrum Disorders. Curr Genet Med Rep. 2014 Sep; 2(3):124-134. View Abstract
  40. Copy number variation plays an important role in clinical epilepsy. Ann Neurol. 2014 Jun; 75(6):943-58. View Abstract
  41. Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment. Neurology. 2013 Jul 30; 81(5):427-30. View Abstract
  42. Density matters: comparison of array platforms for detection of copy-number variation and copy-neutral abnormalities. Genet Med. 2013 Sep; 15(9):706-12. View Abstract
  43. Whole-genome sequencing: ready for prime time? Clin Chem. 2012 Dec; 58(12):1729-30. View Abstract
  44. Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A. 2012 Oct 09; 109(41):16666-71. View Abstract
  45. A prospective study of radiographic manifestations in Hutchinson-Gilford progeria syndrome. Pediatr Radiol. 2012 Sep; 42(9):1089-98. View Abstract
  46. Oligonucleotide microarrays for clinical diagnosis of copy number variation and zygosity status. Curr Protoc Hum Genet. 2012 Jul; Chapter 8:Unit8.12. View Abstract
  47. Phenotypic information in genomic variant databases enhances clinical care and research: the International Standards for Cytogenomic Arrays Consortium experience. Hum Mutat. 2012 May; 33(5):787-96. View Abstract
  48. Exploring concordance and discordance for return of incidental findings from clinical sequencing. Genet Med. 2012 Apr; 14(4):405-10. View Abstract
  49. Mechanisms of premature vascular aging in children with Hutchinson-Gilford progeria syndrome. Hypertension. 2012 Jan; 59(1):92-7. View Abstract
  50. Chromosomal microarray testing influences medical management. Genet Med. 2011 Sep; 13(9):770-6. View Abstract
  51. Age- and gender-dependent obesity in individuals with 16p11.2 deletion. J Genet Genomics. 2011 Sep 20; 38(9):403-9. View Abstract
  52. The adult galactosemic phenotype. J Inherit Metab Dis. 2012 Mar; 35(2):279-86. View Abstract
  53. Hutchinson-Gilford progeria is a skeletal dysplasia. J Bone Miner Res. 2011 Jul; 26(7):1670-9. View Abstract
  54. Cognitive and behavioral characterization of 16p11.2 deletion syndrome. J Dev Behav Pediatr. 2010 Oct; 31(8):649-57. View Abstract
  55. Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders. Am J Med Genet B Neuropsychiatr Genet. 2010 Jun 05; 153B(4):937-47. View Abstract
  56. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010 May 14; 86(5):749-64. View Abstract
  57. Clinical genetic testing for patients with autism spectrum disorders. Pediatrics. 2010 Apr; 125(4):e727-35. View Abstract
  58. Genome-wide oligonucleotide array comparative genomic hybridization for etiological diagnosis of mental retardation: a multicenter experience of 1499 clinical cases. J Mol Diagn. 2010 Mar; 12(2):204-12. View Abstract
  59. Distinct and novel SLC26A4/Pendrin mutations in Chinese and U.S. patients with nonsyndromic hearing loss. Physiol Genomics. 2009 Aug 07; 38(3):281-90. View Abstract
  60. Novel presentation of Omenn syndrome in association with aniridia. J Allergy Clin Immunol. 2009 Apr; 123(4):966-9. View Abstract
  61. Genetic testing for developmental delay: keep searching for an answer. Clin Chem. 2009 Apr; 55(4):827-30; discussion 830-2. View Abstract
  62. Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome. Hum Mutat. 2008 Nov; 29(11):E205-19. View Abstract
  63. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J Med Genet. 2009 Apr; 46(4):242-8. View Abstract
  64. SLC26A4 c.919-2A>G varies among Chinese ethnic groups as a cause of hearing loss. Genet Med. 2008 Aug; 10(8):586-92. View Abstract
  65. Oligonucleotide microarrays for clinical diagnosis of copy number variation. Curr Protoc Hum Genet. 2008 Jul; Chapter 8:Unit 8.12. View Abstract
  66. Oligonucleotide microarrays for clinical diagnosis of copy number variation. Current Protocols in Human Genetics. 2008. View Abstract
  67. Genetic diagnosis of primary immune deficiencies. Immunol Allergy Clin North Am. 2008 May; 28(2):387-412, x. View Abstract
  68. Microduplications of 22q11.2 are frequently inherited and are associated with variable phenotypes. Genet Med. 2008 Apr; 10(4):267-77. View Abstract
  69. Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med. 2008 Feb 14; 358(7):667-75. View Abstract
  70. Development of a focused oligonucleotide-array comparative genomic hybridization chip for clinical diagnosis of genomic imbalance. Clin Chem. 2007 Dec; 53(12):2051-9. View Abstract
  71. Microarray-based CGH detects chromosomal mosaicism not revealed by conventional cytogenetics. Am J Med Genet A. 2007 Aug 01; 143A(15):1679-86. View Abstract
  72. Speech delay and autism spectrum behaviors are frequently associated with duplication of the 7q11.23 Williams-Beuren syndrome region. Genet Med. 2007 Jul; 9(7):427-41. View Abstract
  73. Atherosclerosis: the path from genomics to therapeutics. J Am Coll Cardiol. 2007 Apr 17; 49(15):1589-1599. View Abstract
  74. Influence of genetic variation in the C-reactive protein gene on the inflammatory response during and after acute coronary ischemia. Ann Hum Genet. 2006 Nov; 70(Pt 6):705-16. View Abstract
  75. Genetic determinants of C-reactive protein in COPD. Eur Respir J. 2006 Dec; 28(6):1156-62. View Abstract
  76. Lack of association between genetic variation in 9 innate immunity genes and baseline CRP levels. Ann Hum Genet. 2006 Sep; 70(Pt 5):574-86. View Abstract
  77. Lack of Association Between Genetic Variation in 9 Innate Immunity Genes and Baseline CRP Levels. Ann Hum Genet. 2006 Sep; 70(5):574-586. View Abstract
  78. A prospective assessment of the Y402H variant in complement factor H, genetic variants in C-reactive protein, and risk of age-related macular degeneration. Invest Ophthalmol Vis Sci. 2006 Jun; 47(6):2336-40. View Abstract
  79. Association of common CRP gene variants with CRP levels and cardiovascular events. Ann Hum Genet. 2005 Nov; 69(Pt 6):623-38. View Abstract
  80. Genetics of C-Reactive Protein. CRP: Atherothrombosis and Cardiovascular Risk. P. M. Ridker and N. Rifai, eds. 2005. View Abstract
  81. Case report: a young boy with painful leg swelling. Curr Opin Pediatr. 2002 Dec; 14(6):731-4. View Abstract
  82. The Drosophila primo locus encodes two low-molecular-weight tyrosine phosphatases. Gene. 2000 Feb 08; 243(1-2):1-9. View Abstract
  83. Regulation of EGF receptor signaling establishes pattern across the developing Drosophila retina. Development. 1998 Dec; 125(23):4777-90. View Abstract
  84. Local induction of patterning and programmed cell death in the developing Drosophila retina. Development. 1998 Jun; 125(12):2327-35. View Abstract

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