Research Overview

My lab investigates aberrant cranial motor neuron development by identifying human congenital disorders of eye and face movement, defining their genetic etiologies, and uncovering their molecular pathways and disease mechanisms. Cranial motor neurons provide a unique and powerful system to study neuronal connectivity because of the small number of motor neurons within distinct nuclei and the straightforward tractable trajectories of their axons that can be visualized in three dimensions. Moreover, errors in their development result in visible, reproducible human phenotypes that consistently translate to mouse and zebrafish models.

Our research focuses on genes essential to the development of the cranial nerves, a diverse group of sensory and motor nerves originating in the brain that control our ability to see, hear, taste, smell and carry out a number of other essential functions. Mutations in these genes can cause complex eye-movement disorders, facial weakness, deafness, loss of smell (anosmia), and difficulties with swallowing and respiration. Some individuals with these symptoms may also have other motor, sensory, intellectual, behavioral and social disabilities. My lab has defined the clinical manifestations and identified the genetic causes of a series of such disorders, now referred to as the congenital cranial dysinnervation disorders (CCDDs), including: congenital fibrosis of the extraocular muscles (CFEOM) types 1-3, Duane syndrome, Duane radial ray syndrome, horizontal gaze palsy, and atypical forms of Moebius syndrome. These disorders can result from mutations in genes critical to motor neuron development or that alter the ability of the axon to grow normally, resulting in stalled growth or inappropriate guidance. We have also identified several disorders that selectively impair the development of extraocular or facial muscle.

Major projects in the lab include (1) interpretation of >900 whole genome sequences from families with congenital disorders of eye and face movement, focusing on noncoding and structural variation as well as coding variants; (2) functional and mechanistic studies of genetic variants and their normal and abnormal proteins using mouse and zebrafish modeling, stem cell differentiation to the cell types of interest, and in vitro approaches, (3) studies of embryonic wildtype and mutant cranial motor neurons through single cell RNA sequencing, in situ studies, and mouse and zebrafish gene manipulations. These studies are defining: how these motor neurons acquire distinct identities, form cranial nuclei and subnuclei, and target specific cranial musculature; how these processes are disrupted in human development resulting in birth defects; and why these motor neurons are selectively vulnerable to or spared in specific neurodevelopmental and neurodegenerative disorders.

About Elizabeth Engle

Elizabeth Engle is a Professor of Neurology and Ophthalmology at Harvard Medical School, an Investigator of the Howard Hughes Medical Institute, and an Associate Member of the Broad Institute of MIT and Harvard. At Boston Children's Hospital, she is a member of the Departments of Neurology, Ophthalmology and Medicine (Genetics), a member of the F.M. Kirby Neurobiology Center and the Program in Genomics, and a senior investigator for The Manton Center for Orphan Disease Research. Dr. Engle received her B.A from Middlebury College and her M.D. from Johns Hopkins University School of Medicine. She trained in pediatrics at Johns Hopkins, in neuropathology at Massachusetts General Hospital, and in adult and child neurology in the Longwood Neurology Training Program and at Boston Children's Hospital. Following her residencies, she was a research fellow with Louis Kunkel, Ph.D., and later Alan Beggs, Ph.D., in the Division of Genetics at Children's prior to establishing her own research lab in 1997. Her work has defined the human congenital cranial dysinnervation disorders and has been recognized by high-profile publications and by receipt of multiple honors, including the E. Mead Johnson Award for Research in Pediatrics from the Society for Pediatric Research, the Sidney Carter Award in Child Neurology from the American Academy of Neurology, and a Research Award for Vision from the Alcon Institute. In addition to her research, Dr. Engle continues to care for patients, primarily consulting for children and adults with rare eye and facial movement disorders and other cranial nerve disorders. She teaches in both the clinical and laboratory settings, and has served on multiple committees that set the direction for neuroscience and ophthalmology research locally and nationally.

Researcher Services

Researcher Areas

  • Congenital Eye Movement Disorders
  • Esotropia and Exotropia
  • Genetic Etiologies
  • Motor Neuron Diseases
  • Neurodevelopment
  • Noncoding Etiologies

Research Departments

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PUBLICATIONS

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  1. Dobyns WB, Aldinger KA, Ishak GE, Mirzaa GM, Timms AE, Grout ME, Dremmen MHG, Schot R, Vandervore L, van Slegtenhorst MA, Wilke M, Kasteleijn E, Lee AS, Barry BJ, Chao KR, Szczaluba K, Kobori J, Hanson-Kahn A, Bernstein JA, Carr L, D'Arco F, Miyana K, Okazaki T, Saito Y, Sasaki M, Das S, Wheeler MM, Bamshad MJ, Nickerson DA, Engle EC, Verheijen FW, Doherty D, Mancini GMS. MACF1 Mutations Encoding Highly Conserved Zinc-Binding Residues of the GAR Domain Cause Defects in Neuronal Migration and Axon Guidance. Am J Hum Genet. 2018 Nov 19. View abstract
  2. Grant PE, Im K, Ahtam B, Laurentys CT, Chan WM, Brainard M, Chew S, Drottar M, Robson CD, Drmic I, Engle EC. Altered White Matter Organization in the TUBB3 E410K Syndrome. Cereb Cortex. 2018 Oct 01. View abstract
  3. Whitman MC, Nguyen EH, Bell JL, Tenney AP, Gelber A, Engle EC. Loss of CXCR4/CXCL12 Signaling Causes Oculomotor Nerve Misrouting and Development of Motor Trigeminal to Oculomotor Synkinesis. Invest Ophthalmol Vis Sci. 2018 Oct 01; 59(12):5201-5209. View abstract
  4. Latremoliere A, Cheng L, DeLisle M, Wu C, Chew S, Hutchinson EB, Sheridan A, Alexandre C, Latremoliere F, Sheu SH, Golidy S, Omura T, Huebner EA, Fan Y, Whitman MC, Nguyen E, Hermawan C, Pierpaoli C, Tischfield MA, Woolf CJ, Engle EC. Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration. Cell Rep. 2018 Aug 14; 24(7):1865-1879.e9. View abstract
  5. Shaaban S, MacKinnon S, Andrews C, Staffieri SE, Maconachie GDE, Chan WM, Whitman MC, Morton SU, Yazar S, MacGregor S, Elder JE, Traboulsi EI, Gottlob I, Hewitt AW, Hunter DG, Mackey DA, Engle EC. Genome-Wide Association Study Identifies a Susceptibility Locus for Comitant Esotropia and Suggests a Parent-of-Origin Effect. Invest Ophthalmol Vis Sci. 2018 Aug 01; 59(10):4054-4064. View abstract
  6. Di Gioia SA, Shaaban S, Tüysüz B, Elcioglu NH, Chan WM, Robson CD, Ecklund K, Gilette NM, Hamzaoglu A, Tayfun GA, Traboulsi EI, Engle EC. Recessive MYF5 Mutations Cause External Ophthalmoplegia, Rib, and Vertebral Anomalies. Am J Hum Genet. 2018 Jul 05; 103(1):115-124. View abstract
  7. Marsh APL, Edwards TJ, Galea C, Cooper HM, Engle EC, Jamuar SS, Méneret A, Moutard ML, Nava C, Rastetter A, Robinson G, Rouleau G, Roze E, Spencer-Smith M, Trouillard O, Billette de Villemeur T, Walsh CA, Yu TW, Heron D, Sherr EH, Richards LJ, Depienne C, Leventer RJ, Lockhart PJ. DCC mutation update: Congenital mirror movements, isolated agenesis of the corpus callosum, and developmental split brain syndrome. Hum Mutat. 2018 01; 39(1):23-39. View abstract
  8. Tischfield MA, Robson CD, Gilette NM, Chim SM, Sofela FA, DeLisle MM, Gelber A, Barry BJ, MacKinnon S, Dagi LR, Nathans J, Engle EC. Cerebral Vein Malformations Result from Loss of Twist1 Expression and BMP Signaling from Skull Progenitor Cells and Dura. Dev Cell. 2017 09 11; 42(5):445-461.e5. View abstract
  9. Telegrafi A, Webb BD, Robbins SM, Speck-Martins CE, FitzPatrick D, Fleming L, Redett R, Dufke A, Houge G, van Harssel JJT, Verloes A, Robles A, Manoli I, Engle EC, Jabs EW, Valle D, Carey J, Hoover-Fong JE, Sobreira NLM. Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome. Am J Med Genet A. 2017 Oct; 173(10):2763-2771. View abstract
  10. Whitman MC, Engle EC. Ocular congenital cranial dysinnervation disorders (CCDDs): insights into axon growth and guidance. Hum Mol Genet. 2017 08 01; 26(R1):R37-R44. View abstract
  11. Di Gioia SA, Connors S, Matsunami N, Cannavino J, Rose MF, Gilette NM, Artoni P, de Macena Sobreira NL, Chan WM, Webb BD, Robson CD, Cheng L, Van Ryzin C, Ramirez-Martinez A, Mohassel P, Leppert M, Scholand MB, Grunseich C, Ferreira CR, Hartman T, Hayes IM, Morgan T, Markie DM, Fagiolini M, Swift A, Chines PS, Speck-Martins CE, Collins FS, Jabs EW, Bönnemann CG, Olson EN, Carey JC, Robertson SP, Manoli I, Engle EC. A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome. Nat Commun. 2017 07 06; 8:16077. View abstract
  12. Michalak SM, Whitman MC, Park JG, Tischfield MA, Nguyen EH, Engle EC. Ocular Motor Nerve Development in the Presence and Absence of Extraocular Muscle. Invest Ophthalmol Vis Sci. 2017 04 01; 58(4):2388-2396. View abstract
  13. Nugent AA, Park JG, Wei Y, Tenney AP, Gilette NM, DeLisle MM, Chan WM, Cheng L, Engle EC. Mutant a2-chimaerin signals via bidirectional ephrin pathways in Duane retraction syndrome. J Clin Invest. 2017 May 01; 127(5):1664-1682. View abstract
  14. Jamuar SS, Schmitz-Abe K, D'Gama AM, Drottar M, Chan WM, Peeva M, Servattalab S, Lam AN, Delgado MR, Clegg NJ, Zayed ZA, Dogar MA, Alorainy IA, Jamea AA, Abu-Amero K, Griebel M, Ward W, Lein ES, Markianos K, Barkovich AJ, Robson CD, Grant PE, Bosley TM, Engle EC, Walsh CA, Yu TW. Biallelic mutations in human DCC cause developmental split-brain syndrome. Nat Genet. 2017 Apr; 49(4):606-612. View abstract
  15. Park JG, Tischfield MA, Nugent AA, Cheng L, Di Gioia SA, Chan WM, Maconachie G, Bosley TM, Summers CG, Hunter DG, Robson CD, Gottlob I, Engle EC. Loss of MAFB Function in Humans and Mice Causes Duane Syndrome, Aberrant Extraocular Muscle Innervation, and Inner-Ear Defects. Am J Hum Genet. 2016 06 02; 98(6):1220-1227. View abstract
  16. Brownstein CA, Kleiman RJ, Engle EC, Towne MC, D'Angelo EJ, Yu TW, Beggs AH, Picker J, Fogler JM, Carroll D, Schmitt RC, Wolff RR, Shen Y, Lip V, Bilguvar K, Kim A, Tembulkar S, O'Donnell K, Gonzalez-Heydrich J. 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. View abstract
  17. Whitman MC, Andrews C, Chan WM, Tischfield MA, Stasheff SF, Brancati F, Ortiz-Gonzalez X, Nuovo S, Garaci F, MacKinnon SE, Hunter DG, Grant PE, Engle EC. Two unique TUBB3 mutations cause both CFEOM3 and malformations of cortical development. Am J Med Genet A. 2016 Feb; 170A(2):297-305. View abstract
  18. Balasubramanian R, Chew S, MacKinnon SE, Kang PB, Andrews C, Chan WM, Engle EC. Expanding the phenotypic spectrum and variability of endocrine abnormalities associated with TUBB3 E410K syndrome. J Clin Endocrinol Metab. 2015 Mar; 100(3):E473-7. View abstract
  19. Smpokou P, Samanta M, Berry GT, Hecht L, Engle EC, Lichter-Konecki U. Menkes disease in affected females: the clinical disease spectrum. Am J Med Genet A. 2015 Feb; 167A(2):417-20. View abstract
  20. Khan AO, Almutlaq M, Oystreck DT, Engle EC, Abu-Amero K, Bosley T. Retinal Dysfunction in Patients with Congenital Fibrosis of the Extraocular Muscles Type 2. Ophthalmic Genet. 2016 06; 37(2):130-6. View abstract
  21. Cheng L, Desai J, Miranda CJ, Duncan JS, Qiu W, Nugent AA, Kolpak AL, Wu CC, Drokhlyansky E, Delisle MM, Chan WM, Wei Y, Propst F, Reck-Peterson SL, Fritzsch B, Engle EC. Human CFEOM1 mutations attenuate KIF21A autoinhibition and cause oculomotor axon stalling. Neuron. 2014 Apr 16; 82(2):334-49. View abstract
  22. MacKinnon S, Oystreck DT, Andrews C, Chan WM, Hunter DG, Engle EC. Diagnostic distinctions and genetic analysis of patients diagnosed with moebius syndrome. Ophthalmology. 2014 Jul; 121(7):1461-8. View abstract
  23. Irahara K, Saito Y, Sugai K, Nakagawa E, Saito T, Komaki H, Nakata Y, Sato N, Baba K, Yamamoto T, Chan WM, Andrews C, Engle EC, Sasaki M. Pontine malformation, undecussated pyramidal tracts, and regional polymicrogyria: a new syndrome. Pediatr Neurol. 2014 Apr; 50(4):384-8. View abstract
  24. Shaaban S, Ramos-Platt L, Gilles FH, Chan WM, Andrews C, De Girolami U, Demer J, Engle EC. RYR1 mutations as a cause of ophthalmoplegia, facial weakness, and malignant hyperthermia. JAMA Ophthalmol. 2013 Dec; 131(12):1532-40. View abstract
  25. Baris HN, Chan WM, Andrews C, Behar DM, Donovan DJ, Morton CC, Ranells J, Pal T, Ligon AH, Engle EC. Complex cytogenetic rearrangements at the DURS1 locus in syndromic Duane retraction syndrome. Clin Case Rep. 2013 Oct 01; 1(1). View abstract
  26. Graeber CP, Hunter DG, Engle EC. The genetic basis of incomitant strabismus: consolidation of the current knowledge of the genetic foundations of disease. Semin Ophthalmol. 2013 Sep-Nov; 28(5-6):427-37. View abstract
  27. Thomas S, Thomas MG, Andrews C, Chan WM, Proudlock FA, McLean RJ, Pradeep A, Engle EC, Gottlob I. Autosomal-dominant nystagmus, foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation. Eur J Hum Genet. 2014 Mar; 22(3):344-9. View abstract
  28. Shaaban S, Duzcan F, Yildirim C, Chan WM, Andrews C, Akarsu NA, Engle EC. Expanding the phenotypic spectrum of ECEL1-related congenital contracture syndromes. Clin Genet. 2014 Jun; 85(6):562-7. View abstract
  29. Chew S, Balasubramanian R, Chan WM, Kang PB, Andrews C, Webb BD, MacKinnon SE, Oystreck DT, Rankin J, Crawford TO, Geraghty M, Pomeroy SL, Crowley WF, Jabs EW, Hunter DG, Grant PE, Engle EC. A novel syndrome caused by the E410K amino acid substitution in the neuronal ß-tubulin isotype 3. Brain. 2013 Feb; 136(Pt 2):522-35. View abstract
  30. Cederquist GY, Luchniak A, Tischfield MA, Peeva M, Song Y, Menezes MP, Chan WM, Andrews C, Chew S, Jamieson RV, Gomes L, Flaherty M, Grant PE, Gupta ML, Engle EC. An inherited TUBB2B mutation alters a kinesin-binding site and causes polymicrogyria, CFEOM and axon dysinnervation. Hum Mol Genet. 2012 Dec 15; 21(26):5484-99. View abstract
  31. Webb BD, Shaaban S, Gaspar H, Cunha LF, Schubert CR, Hao K, Robson CD, Chan WM, Andrews C, MacKinnon S, Oystreck DT, Hunter DG, Iacovelli AJ, Ye X, Camminady A, Engle EC, Jabs EW. HOXB1 founder mutation in humans recapitulates the phenotype of Hoxb1-/- mice. Am J Hum Genet. 2012 Jul 13; 91(1):171-9. View abstract
  32. Desai J, Velo MP, Yamada K, Overman LM, Engle EC. Spatiotemporal expression pattern of KIF21A during normal embryonic development and in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). Gene Expr Patterns. 2012 May-Jun; 12(5-6):180-8. View abstract
  33. Nugent AA, Kolpak AL, Engle EC. Human disorders of axon guidance. Curr Opin Neurobiol. 2012 Oct; 22(5):837-43. View abstract
  34. Garcia-Martin E, Pinilla I, Almarcegui C, Fernandez J, Engle EC, Ramos FJ. Ocular manifestations (strabismus: duane syndrome; and retinal nerve fiber hypoplasia) in okihiro syndrome (duane radial ray syndrome). Binocul Vis Strabolog Q Simms Romano. 2012; 27(4):235-42. View abstract
  35. VanderVeen DK, Andrews C, Nihalani BR, Engle EC. Crystalline cataract caused by a heterozygous missense mutation in ?D-crystallin (CRYGD). Mol Vis. 2011; 17:3333-8. View abstract
  36. Högen T, Chan WM, Riedel E, Brüning R, Chang HH, Engle EC, Danek A. Wildervanck's syndrome and mirror movements: a congenital disorder of axon migration? J Neurol. 2012 Apr; 259(4):761-3. View abstract
  37. Miyake N, Demer JL, Shaaban S, Andrews C, Chan WM, Christiansen SP, Hunter DG, Engle EC. Expansion of the CHN1 strabismus phenotype. Invest Ophthalmol Vis Sci. 2011 Aug 11; 52(9):6321-8. View abstract
  38. Chan WM, Miyake N, Zhu-Tam L, Andrews C, Engle EC. Two novel CHN1 mutations in 2 families with Duane retraction syndrome. Arch Ophthalmol. 2011 May; 129(5):649-52. View abstract
  39. Thomas MG, Kumar A, Mohammad S, Proudlock FA, Engle EC, Andrews C, Chan WM, Thomas S, Gottlob I. Structural grading of foveal hypoplasia using spectral-domain optical coherence tomography a predictor of visual acuity? Ophthalmology. 2011 Aug; 118(8):1653-60. View abstract
  40. Oystreck DT, Engle EC, Bosley TM. Recent progress in understanding congenital cranial dysinnervation disorders. J Neuroophthalmol. 2011 Mar; 31(1):69-77. View abstract
  41. Tischfield MA, Cederquist GY, Gupta ML, Engle EC. Phenotypic spectrum of the tubulin-related disorders and functional implications of disease-causing mutations. Curr Opin Genet Dev. 2011 Jun; 21(3):286-94. View abstract
  42. Walsh CA, Engle EC. Allelic diversity in human developmental neurogenetics: insights into biology and disease. Neuron. 2010 Oct 21; 68(2):245-53. View abstract
  43. Yang X, Yamada K, Katz B, Guan H, Wang L, Andrews C, Zhao G, Engle EC, Chen H, Tong Z, Kong J, Hu C, Kong Q, Fan G, Wang Z, Ning M, Zhang S, Xu J, Zhang K. KIF21A mutations in two Chinese families with congenital fibrosis of the extraocular muscles (CFEOM). Mol Vis. 2010 Oct 13; 16:2062-70. View abstract
  44. Ching MS, Shen Y, Tan WH, Jeste SS, Morrow EM, Chen X, Mukaddes NM, Yoo SY, Hanson E, Hundley R, Austin C, Becker RE, Berry GT, Driscoll K, Engle EC, Friedman S, Gusella JF, Hisama FM, Irons MB, Lafiosca T, LeClair E, Miller DT, Neessen M, Picker JD, Rappaport L, Rooney CM, Sarco DP, Stoler JM, Walsh CA, Wolff RR, Zhang T, Nasir RH, Wu BL. 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
  45. Tischfield MA, Engle EC. Distinct alpha- and beta-tubulin isotypes are required for the positioning, differentiation and survival of neurons: new support for the 'multi-tubulin' hypothesis. Biosci Rep. 2010 Apr 15; 30(5):319-30. View abstract
  46. Demer JL, Clark RA, Tischfield MA, Engle EC. Evidence of an asymmetrical endophenotype in congenital fibrosis of extraocular muscles type 3 resulting from TUBB3 mutations. Invest Ophthalmol Vis Sci. 2010 Sep; 51(9):4600-11. View abstract
  47. Engle EC. Human genetic disorders of axon guidance. Cold Spring Harb Perspect Biol. 2010 Mar; 2(3):a001784. View abstract
  48. Rankin JK, Andrews C, Chan WM, Engle EC. HOXA1 mutations are not a common cause of Möbius syndrome. J AAPOS. 2010 Feb; 14(1):78-80. View abstract
  49. Tischfield MA, Baris HN, Wu C, Rudolph G, Van Maldergem L, He W, Chan WM, Andrews C, Demer JL, Robertson RL, Mackey DA, Ruddle JB, Bird TD, Gottlob I, Pieh C, Traboulsi EI, Pomeroy SL, Hunter DG, Soul JS, Newlin A, Sabol LJ, Doherty EJ, de Uzcátegui CE, de Uzcátegui N, Collins ML, Sener EC, Wabbels B, Hellebrand H, Meitinger T, de Berardinis T, Magli A, Schiavi C, Pastore-Trossello M, Koc F, Wong AM, Levin AV, Geraghty MT, Descartes M, Flaherty M, Jamieson RV, Møller HU, Meuthen I, Callen DF, Kerwin J, Lindsay S, Meindl A, Gupta ML, Pellman D, Engle EC. Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell. 2010 Jan 08; 140(1):74-87. View abstract
  50. Miyake N, Andrews C, Fan W, He W, Chan WM, Engle EC. CHN1 mutations are not a common cause of sporadic Duane's retraction syndrome. Am J Med Genet A. 2010 Jan; 152A(1):215-7. View abstract
  51. Oystreck DT, Khan AO, Vila-Coro AA, Oworu O, Al-Tassan N, Chan WM, Engle EC, Bosley TM. Synergistic divergence: a distinct ocular motility dysinnervation pattern. Invest Ophthalmol Vis Sci. 2009 Nov; 50(11):5213-6. View abstract
  52. Murillo-Correa CE, Kon-Jara V, Engle EC, Zenteno JC. Clinical features associated with an I126M alpha2-chimaerin mutation in a family with autosomal-dominant Duane retraction syndrome. J AAPOS. 2009 Jun; 13(3):245-8. View abstract
  53. Flaherty MP, Balachandran C, Jamieson R, Engle EC. Congenital fibrosis of the extraocular muscles type 1, distinctive conjunctival changes and intrapapillary disc colobomata. Ophthalmic Genet. 2009 Jun; 30(2):91-5. View abstract
  54. Miyake N, Chilton J, Psatha M, Cheng L, Andrews C, Chan WM, Law K, Crosier M, Lindsay S, Cheung M, Allen J, Gutowski NJ, Ellard S, Young E, Iannaccone A, Appukuttan B, Stout JT, Christiansen S, Ciccarelli ML, Baldi A, Campioni M, Zenteno JC, Davenport D, Mariani LE, Sahin M, Guthrie S, Engle EC. Human CHN1 mutations hyperactivate alpha2-chimaerin and cause Duane's retraction syndrome. Science. 2008 Aug 08; 321(5890):839-43. View abstract
  55. Bosley TM, Alorainy IA, Salih MA, Aldhalaan HM, Abu-Amero KK, Oystreck DT, Tischfield MA, Engle EC, Erickson RP. The clinical spectrum of homozygous HOXA1 mutations. Am J Med Genet A. 2008 May 15; 146A(10):1235-40. View abstract
  56. Dumars S, Andrews C, Chan WM, Engle EC, Demer JL. Magnetic resonance imaging of the endophenotype of a novel familial Möbius-like syndrome. J AAPOS. 2008 Aug; 12(4):381-9. View abstract
  57. Heidary G, Engle EC, Hunter DG. Congenital fibrosis of the extraocular muscles. Semin Ophthalmol. 2008 Jan-Feb; 23(1):3-8. View abstract
  58. Demer JL, Clark RA, Lim KH, Engle EC. Magnetic resonance imaging of innervational and extraocular muscle abnormalities in Duane-radial ray syndrome. Invest Ophthalmol Vis Sci. 2007 Dec; 48(12):5505-11. View abstract
  59. Bosley TM, Salih MA, Alorainy IA, Oystreck DT, Nester M, Abu-Amero KK, Tischfield MA, Engle EC. Clinical characterization of the HOXA1 syndrome BSAS variant. Neurology. 2007 Sep 18; 69(12):1245-53. View abstract
  60. Chan WM, Andrews C, Dragan L, Fredrick D, Armstrong L, Lyons C, Geraghty MT, Hunter DG, Yazdani A, Traboulsi EI, Pott JW, Gutowski NJ, Ellard S, Young E, Hanisch F, Koc F, Schnall B, Engle EC. Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1. BMC Genet. 2007 May 18; 8:26. View abstract
  61. Engle EC. Oculomotility disorders arising from disruptions in brainstem motor neuron development. Arch Neurol. 2007 May; 64(5):633-7. View abstract
  62. Lim KH, Engle EC, Demer JL. Abnormalities of the oculomotor nerve in congenital fibrosis of the extraocular muscles and congenital oculomotor palsy. Invest Ophthalmol Vis Sci. 2007 Apr; 48(4):1601-6. View abstract
  63. Engle EC. Genetic basis of congenital strabismus. Arch Ophthalmol. 2007 Feb; 125(2):189-95. View abstract
  64. Engle EC, Andrews C, Law K, Demer JL. Two pedigrees segregating Duane's retraction syndrome as a dominant trait map to the DURS2 genetic locus. Invest Ophthalmol Vis Sci. 2007 Jan; 48(1):189-93. View abstract
  65. Demer JL, Clark RA, Lim KH, Engle EC. Magnetic resonance imaging evidence for widespread orbital dysinnervation in dominant Duane's retraction syndrome linked to the DURS2 locus. Invest Ophthalmol Vis Sci. 2007 Jan; 48(1):194-202. View abstract
  66. Sicotte NL, Salamon G, Shattuck DW, Hageman N, Rüb U, Salamon N, Drain AE, Demer JL, Engle EC, Alger JR, Baloh RW, Deller T, Jen JC. Diffusion tensor MRI shows abnormal brainstem crossing fibers associated with ROBO3 mutations. Neurology. 2006 Aug 08; 67(3):519-21. View abstract
  67. Bosley TM, Oystreck DT, Robertson RL, al Awad A, Abu-Amero K, Engle EC. Neurological features of congenital fibrosis of the extraocular muscles type 2 with mutations in PHOX2A. Brain. 2006 Sep; 129(Pt 9):2363-74. View abstract
  68. Tischfield MA, Chan WM, Grunert JF, Andrews C, Engle EC. HOXA1 mutations are not a common cause of Duane anomaly. Am J Med Genet A. 2006 Apr 15; 140(8):900-2. View abstract
  69. Demer JL, Ortube MC, Engle EC, Thacker N. High-resolution magnetic resonance imaging demonstrates abnormalities of motor nerves and extraocular muscles in patients with neuropathic strabismus. J AAPOS. 2006 Apr; 10(2):135-42. View abstract
  70. Engle EC. The genetic basis of complex strabismus. Pediatr Res. 2006 Mar; 59(3):343-8. View abstract
  71. Chan WM, Traboulsi EI, Arthur B, Friedman N, Andrews C, Engle EC. Horizontal gaze palsy with progressive scoliosis can result from compound heterozygous mutations in ROBO3. J Med Genet. 2006 Mar; 43(3):e11. View abstract
  72. Tischfield MA, Bosley TM, Salih MA, Alorainy IA, Sener EC, Nester MJ, Oystreck DT, Chan WM, Andrews C, Erickson RP, Engle EC. Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development. Nat Genet. 2005 Oct; 37(10):1035-7. View abstract
  73. Yamada K, Hunter DG, Andrews C, Engle EC. A novel KIF21A mutation in a patient with congenital fibrosis of the extraocular muscles and Marcus Gunn jaw-winking phenomenon. Arch Ophthalmol. 2005 Sep; 123(9):1254-9. View abstract
  74. Demer JL, Clark RA, Engle EC. Magnetic resonance imaging evidence for widespread orbital dysinnervation in congenital fibrosis of extraocular muscles due to mutations in KIF21A. Invest Ophthalmol Vis Sci. 2005 Feb; 46(2):530-9. View abstract
  75. Traboulsi EI, Engle EC. Mutations in KIF21A are responsible for CFEOM1 worldwide. Ophthalmic Genet. 2004 Dec; 25(4):237-9. View abstract
  76. Yamada K, Chan WM, Andrews C, Bosley TM, Sener EC, Zwaan JT, Mullaney PB, Oztürk BT, Akarsu AN, Sabol LJ, Demer JL, Sullivan TJ, Gottlob I, Roggenkäemper P, Mackey DA, De Uzcategui CE, Uzcategui N, Ben-Zeev B, Traboulsi EI, Magli A, de Berardinis T, Gagliardi V, Awasthi-Patney S, Vogel MC, Rizzo JF, Engle EC. Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3). Invest Ophthalmol Vis Sci. 2004 Jul; 45(7):2218-23. View abstract
  77. Jen JC, Chan WM, Bosley TM, Wan J, Carr JR, Rüb U, Shattuck D, Salamon G, Kudo LC, Ou J, Lin DD, Salih MA, Kansu T, Al Dhalaan H, Al Zayed Z, MacDonald DB, Stigsby B, Plaitakis A, Dretakis EK, Gottlob I, Pieh C, Traboulsi EI, Wang Q, Wang L, Andrews C, Yamada K, Demer JL, Karim S, Alger JR, Geschwind DH, Deller T, Sicotte NL, Nelson SF, Baloh RW, Engle EC. Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis. Science. 2004 Jun 04; 304(5676):1509-13. View abstract
  78. Yamada K, Andrews C, Chan WM, McKeown CA, Magli A, de Berardinis T, Loewenstein A, Lazar M, O'Keefe M, Letson R, London A, Ruttum M, Matsumoto N, Saito N, Morris L, Del Monte M, Johnson RH, Uyama E, Houtman WA, de Vries B, Carlow TJ, Hart BL, Krawiecki N, Shoffner J, Vogel MC, Katowitz J, Goldstein SM, Levin AV, Sener EC, Ozturk BT, Akarsu AN, Brodsky MC, Hanisch F, Cruse RP, Zubcov AA, Robb RM, Roggenkäemper P, Gottlob I, Kowal L, Battu R, Traboulsi EI, Franceschini P, Newlin A, Demer JL, Engle EC. Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). Nat Genet. 2003 Dec; 35(4):318-21. View abstract
  79. Yazdani A, Chung DC, Abbaszadegan MR, Al-Khayer K, Chan WM, Yazdani M, Ghodsi K, Engle EC, Traboulsi EI. A novel PHOX2A/ARIX mutation in an Iranian family with congenital fibrosis of extraocular muscles type 2 (CFEOM2). Am J Ophthalmol. 2003 Nov; 136(5):861-5. View abstract
  80. Gutowski NJ, Bosley TM, Engle EC. 110th ENMC International Workshop: the congenital cranial dysinnervation disorders (CCDDs). Naarden, The Netherlands, 25-27 October, 2002. Neuromuscul Disord. 2003 Sep; 13(7-8):573-8. View abstract
  81. Uyama E, Yamada K, Kawano H, Chan WM, Andrews C, Yoshioka M, Uchino M, Engle EC. A Japanese family with FEOM1-linked congenital fibrosis of the extraocular muscles type 1 associated with spinal canal stenosis and refinement of the FEOM1 critical region. Neuromuscul Disord. 2003 Aug; 13(6):472-8. View abstract
  82. Pieh C, Goebel HH, Engle EC, Gottlob I. Congenital fibrosis syndrome associated with central nervous system abnormalities. Graefes Arch Clin Exp Ophthalmol. 2003 Jul; 241(7):546-553. View abstract
  83. Ryan MM, Engle EC. Acute ataxia in childhood. J Child Neurol. 2003 May; 18(5):309-16. View abstract
  84. Al-Baradie R, Yamada K, St Hilaire C, Chan WM, Andrews C, McIntosh N, Nakano M, Martonyi EJ, Raymond WR, Okumura S, Okihiro MM, Engle EC. Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. Am J Hum Genet. 2002 Nov; 71(5):1195-9. View abstract
  85. Iannaccone A, McIntosh N, Ciccarelli ML, Baldi A, Mutolo PA, Tedesco SA, Engle EC. Familial unilateral Brown syndrome. Ophthalmic Genet. 2002 Sep; 23(3):175-84. View abstract
  86. Gottlob I, Jain S, Engle EC. Elevation of one eye during tooth brushing. Am J Ophthalmol. 2002 Sep; 134(3):459-60. View abstract
  87. Engle EC, Leigh RJ. Genes, brainstem development, and eye movements. Neurology. 2002 Aug 13; 59(3):304-5. View abstract
  88. Engle EC. The molecular basis of the congenital fibrosis syndromes. Strabismus. 2002 Jun; 10(2):125-8. View abstract
  89. Engle EC. Applications of molecular genetics to the understanding of congenital ocular motility disorders. Ann N Y Acad Sci. 2002 Apr; 956:55-63. View abstract
  90. Mackey DA, Chan WM, Chan C, Gillies WE, Brooks AM, O'Day J, Engle EC. Congenital fibrosis of the vertically acting extraocular muscles maps to the FEOM3 locus. Hum Genet. 2002 May; 110(5):510-2. View abstract
  91. Engle EC, McIntosh N, Yamada K, Lee BA, Johnson R, O'Keefe M, Letson R, London A, Ballard E, Ruttum M, Matsumoto N, Saito N, Collins ML, Morris L, Del Monte M, Magli A, de Berardinis T. CFEOM1, the classic familial form of congenital fibrosis of the extraocular muscles, is genetically heterogeneous but does not result from mutations in ARIX. BMC Genet. 2002; 3:3. View abstract
  92. Nakano M, Yamada K, Fain J, Sener EC, Selleck CJ, Awad AH, Zwaan J, Mullaney PB, Bosley TM, Engle EC. Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of the extraocular muscles type 2. Nat Genet. 2001 Nov; 29(3):315-20. View abstract
  93. Flaherty MP, Grattan-Smith P, Steinberg A, Jamieson R, Engle EC. Congenital fibrosis of the extraocular muscles associated with cortical dysplasia and maldevelopment of the basal ganglia. Ophthalmology. 2001 Jul; 108(7):1313-22. View abstract
  94. O'Brien KF, Engle EC, Kunkel LM. Analysis of human sarcospan as a candidate gene for CFEOM1. BMC Genet. 2001; 2:3. View abstract
  95. Shivaram SM, Engle EC, Petersen RA, Robb RM. Congenital fibrosis syndromes. Int Ophthalmol Clin. 2001; 41(4):105-13. View abstract
  96. Sener EC, Lee BA, Turgut B, Akarsu AN, Engle EC. A clinically variant fibrosis syndrome in a Turkish family maps to the CFEOM1 locus on chromosome 12. Arch Ophthalmol. 2000 Aug; 118(8):1090-7. View abstract
  97. Traboulsi EI, Lee BA, Mousawi A, Khamis AR, Engle EC. Evidence of genetic heterogeneity in autosomal recessive congenital fibrosis of the extraocular muscles. Am J Ophthalmol. 2000 May; 129(5):658-62. View abstract
  98. Doherty EJ, Macy ME, Wang SM, Dykeman CP, Melanson MT, Engle EC. CFEOM3: a new extraocular congenital fibrosis syndrome that maps to 16q24.2-q24.3. Invest Ophthalmol Vis Sci. 1999 Jul; 40(8):1687-94. View abstract
  99. Engle E. A genetic approach to congenital extraocular muscle disorders. J Child Neurol. 1999 Jan; 14(1):34-7. View abstract
  100. Wang SM, Zwaan J, Mullaney PB, Jabak MH, Al-Awad A, Beggs AH, Engle EC. Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13. Am J Hum Genet. 1998 Aug; 63(2):517-25. View abstract
  101. Swoboda KJ, Engle EC, Scheindlin B, Anthony DC, Jones HR. Mutilating hand syndrome in an infant with familial carpal tunnel syndrome. Muscle Nerve. 1998 Jan; 21(1):104-11. View abstract
  102. Engle EC, Castro AE, Macy ME, Knoll JH, Beggs AH. A gene for isolated congenital ptosis maps to a 3-cM region within 1p32-p34.1. Am J Hum Genet. 1997 May; 60(5):1150-7. View abstract
  103. Engle EC, Goumnerov BC, McKeown CA, Schatz M, Johns DR, Porter JD, Beggs AH. Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles. Ann Neurol. 1997 Mar; 41(3):314-25. View abstract
  104. Engle EC, Marondel I, Houtman WA, de Vries B, Loewenstein A, Lazar M, Ward DC, Kucherlapati R, Beggs AH. Congenital fibrosis of the extraocular muscles (autosomal dominant congenital external ophthalmoplegia): genetic homogeneity, linkage refinement, and physical mapping on chromosome 12. Am J Hum Genet. 1995 Nov; 57(5):1086-94. View abstract
  105. Khurana TS, Engle EC, Bennett RR, Silverman GA, Selig S, Bruns GA, Kunkel LM. (CA) repeat polymorphism in the chromosome 18 encoded dystrophin-like protein. Hum Mol Genet. 1994 May; 3(5):841. View abstract
  106. Engle EC, Kunkel LM, Specht LA, Beggs AH. Mapping a gene for congenital fibrosis of the extraocular muscles to the centromeric region of chromosome 12. Nat Genet. 1994 May; 7(1):69-73. View abstract
  107. Dangond F, Engle E, Yessayan L, Sawyer MH. Pre-eruptive varicella cerebellitis confirmed by PCR. Pediatr Neurol. 1993 Nov-Dec; 9(6):491-3. View abstract
  108. Petri M, Genovese M, Engle E, Hochberg M. Definition, incidence, and clinical description of flare in systemic lupus erythematosus. A prospective cohort study. Arthritis Rheum. 1991 Aug; 34(8):937-44. View abstract
  109. Engle EC, Manes SH, Drlica K. Differential effects of antibiotics inhibiting gyrase. J Bacteriol. 1982 Jan; 149(1):92-8. View abstract
  110. Drlica K, Engle EC, Manes SH. DNA gyrase on the bacterial chromosome: possibility of two levels of action. Proc Natl Acad Sci U S A. 1980 Nov; 77(11):6879-83. View abstract