NeuroMolecular Medicine

, Volume 10, Issue 3, pp 148–156 | Cite as

The Molecular Basis of Familial Dysautonomia: Overview, New Discoveries and Implications for Directed Therapies

Original Paper


Familial dysautonomia (FD) is a sensory and autonomic neuropathy that affects the development and survival of sensory, sympathetic, and some parasympathetic neurons. It is autosomally inherited and occurs almost exclusively among individuals of Ashkenazi Jewish descent. The pathological and clinical manisfestations of FD have been extensively studied and therapeutic modalities have, until recently, focused primarily on addressing the symptoms experienced by those with this fatal disorder. The primary FD-causing mutation is an intronic nucleotide substitution that alters the splicing of the IKBKAP-derived transcript. Recent efforts have resulted in the development of new therapeutic modalities that facilitate the increased production of the correctly spliced transcript and mitigate the symptoms of those with FD. Furthermore, the recent demonstration of the reduced presence of monoamine oxidase A in cells and tissues of individuals with FD has provided new insight into the cause of hypertensive crises experienced by these patients.


Autonomic nervous system Familial dysautonomia IKAP IKBKAP Monoamine oxidase RNA splicing 



Dr. Anderson's salary was supported by a grant from Familial Dysautonomia Hope, Inc.


  1. Aguayo, A. J., Nair, C. P., & Bray, G. M. (1971). Peripheral nerve abnormalities in the Riley-Day syndrome. Findings in a sural nerve biopsy. Archives of Neurology, 24, 106–116.PubMedGoogle Scholar
  2. Albanese, S. A., & Bobechko, W. P. (1987). Spine deformity in familial dysautonomia (Riley-Day syndrome). Journal of Pediatric Orthopedics, 7, 179–183.PubMedGoogle Scholar
  3. Anderson, S. L., Coli, R., Daly, I. W., Kichula, E. A., Rork, M. J., Volpi, S. A., Ekstein, J., & Rubin, B. Y. (2001). Familial dysautonomia is caused by mutations of the IKAP gene. American Journal of Human Genetics, 68, 753–758.PubMedCrossRefGoogle Scholar
  4. Anderson, M. C., Hasan, F., McCrodden, J. M., & Tipton, K. F. (1993). Monoamine oxidase inhibitors and the cheese effect. Neurochemical Research, 18, 1145–1149.PubMedCrossRefGoogle Scholar
  5. Anderson, S. L., Qiu, J., & Rubin, B. Y. (2003a). Tocotrienols induce IKBKAP expression: A possible therapy for familial dysautonomia. Biochemical and Biophysical Research Communications, 306, 303–309.PubMedCrossRefGoogle Scholar
  6. Anderson, S. L., Qiu, J., & Rubin, B. Y. (2003b). EGCG corrects aberrant splicing of IKAP mRNA in cells from patients with familial dysautonomia. Biochemical and Biophysical Research Communications, 310, 627–633.PubMedCrossRefGoogle Scholar
  7. Anderson, S. L., & Rubin, B. Y. (2005). Tocotrienols reverse IKAP and monoamine oxidase deficiencies in familial dysautonomia. Biochemical and Biophysical Research Communications, 336, 150–156.PubMedCrossRefGoogle Scholar
  8. Axelrod, F. B. (2002) Hereditary sensory and autonomic neuropathies. Familial dysautonomia and other HSANs. Clinical Autonomic Research, Suppl 1, I2–14.Google Scholar
  9. Axelrod, F. B. (2004). Familial dysautonomia. Muscle Nerve, 29, 352–363.PubMedCrossRefGoogle Scholar
  10. Axelrod, F. B., Goldberg, J. D., Rolnitzky, L., Mull, J., Mann, S. P., Gold von Simson, G., Berlin, D., & Slaugenhaupt, S. A. (2005). Fludrocortisone in patients with familial dysautonomia–assessing effect on clinical parameters and gene expression. Clinical Autonomic Research, 15, 284–291.PubMedCrossRefGoogle Scholar
  11. Axelrod, F. B., Goldstein, D. S., Holmes, C., Berlin, D., & Kopin, I. J. (1996). Pattern of plasma levels of catecholamines in familial dysautonomia. Clinical Autonomic Research, 6, 205–209.PubMedCrossRefGoogle Scholar
  12. Axelrod, F. B., Gouge, T. H., Ginsburg, H. B., Bangaru, B. S., & Hazzi, C. (1991). Fundoplication and gastrostomy in familial dysautonomia. Journal of Pediatrics, 118, 388–394.PubMedCrossRefGoogle Scholar
  13. Axelrod, F. B., Iyer, K., Fish, I., Pearson, J., Sein, M. E., & Spielholz, N. (1981). Progressive sensory loss in familial dysautonomia. Pediatrics, 67, 517–522.PubMedGoogle Scholar
  14. Axelrod, F. B., Zupanc, M., Hilz, M. J., & Kramer, E. L. (2000). Ictal SPECT during autonomic crisis in familial dysautonomia. Neurology, 55, 122–125.PubMedGoogle Scholar
  15. Bar-Shai, A., Maayan, C., Vromen, A., Udassin, R., Nissan, A., Freund, H. R., & Hanani, M. (2004). Decreased density of ganglia and neurons in the myenteric plexus of familial dysautonomia patients. Journal of the Neurological Sciences, 220, 89–94.PubMedCrossRefGoogle Scholar
  16. Beck, S., Penque, D., Garcia, S., Gomes A., Farinha, C., Mata, L., Gulbenkian S., Gil-Ferreira, K., Duarte, A., Pacheco, P., Barreto, C., Lopes, B., Cavaco, J., Lavinha, J., & Amaral, M. D. (1999). Cystic fibrosis patients with the 3272-26A→G mutation have mild disease, leaky alternative mRNA splicing, and CFTR protein at the cell membrane. Human Mutation, 14, 133–144.PubMedCrossRefGoogle Scholar
  17. Bernardi, L., Hilz, M., Stemper, B., Passino, C., Welsch, G., & Axelrod, F. B. (2003). Respiratory and cerebrovascular responses to hypoxia and hypercapnia in familial dysautonomia. American Journal of Respiratory and Critical Care Medicine, 167, 141–149.PubMedCrossRefGoogle Scholar
  18. Bickel, A., Axelrod, F. B., Schmelz, M., Marthol, H., & Hilz, M. J. (2002). Dermal microdialysis provides evidence for hypersensitivity to noradrenaline in patients with familial dysautonomia. Journal of Neurology, Neurosurgery, and Psychiatry, 73, 299–302.PubMedCrossRefGoogle Scholar
  19. Blackwell, B. (1963). Hypertensive crisis due to monoamine-oxidase inhibitors. Lancet, 2, 849–850.PubMedCrossRefGoogle Scholar
  20. Blackwell, B., Marley, E., & Ryle, A. (1964). Hypertensive crisis associated with monoamine-oxidase inhibitors. Lancet, 1, 722–723.PubMedCrossRefGoogle Scholar
  21. Blumenfeld, A., Slaugenhaupt, S. A., Axelrod, F. B., Lucente, D. E., Maayan, C., Liebert, C. B., Ozelius, L. J., Trofatter, J. A., Haines, J. L., Breakefield, X. O., et al. (1993). Localization of the gene for familial dysautonomia on chromosome 9 and definition of DNA markers for genetic diagnosis. Nature Genetics, 4, 160–164.PubMedCrossRefGoogle Scholar
  22. Blumenfeld, A., Slaugenhaupt, S. A., Liebert, C. B., Temper, V., Maayan, C., Gill, S., Lucente, D. E., Idelson, M., MacCormack, K., Monahan, M. A., Mull, J., Leyne, M., Mendillo, M., Schiripo, T., Mishori, E., Breakefield, X., Axelrod, F. B., & Gusella, J. F. (1999). Precise genetic mapping and haplotype analysis of the familial dysautonomia gene on human chromosome 9q31. American Journal of Human Genetics, 64, 1110–1118.PubMedCrossRefGoogle Scholar
  23. Boerkoel, C. F., Exelbert, R., Nicastri, C., Nichols, R. C., Miller, F. W., Plotz, P. H., & Raben, N. (1995). Leaky splicing mutation in the acid maltase gene is associated with delayed onset of glycogenosis type II. American Journal of Human Genetics, 56, 887–897.PubMedGoogle Scholar
  24. Brown, C. M., Stemper, B., Welsch, G., Brys, M., Axelrod, F. B., & Hilz, M.J. (2003). Orthostatic challenge reveals impaired vascular resistance control, but normal venous pooling and capillary filtration in familial dysautonomia. Clinical Science (London), 104, 163–169.Google Scholar
  25. Brunt, P. W., & McKusick, V. A. (1970). Familial dysautonomia. A report of genetic and clinical studies, with a review of the literature. Medicine (Baltimore), 49, 343–374.Google Scholar
  26. Challands, J. F., & Facer, E. K. (1998). Epidural anaesthesia and familial dysautonomia (the Riley Day syndrome). Three case reports. Paediatric Anaesthesia, 8, 83–88.PubMedCrossRefGoogle Scholar
  27. Close, P., Hawkes, N., Cornez, I., Creppe, C., Lambert, C. A., Rogister, B., Siebenlist, U., Merville, M. P., Slaugenhaupt, S. A., Bours, V., Svejstrup, J. Q., & Chariot, A. (2006). Transcription impairment and cell migration defects in elongator-depleted cells: Implication for familial dysautonomia. Molecular Cell, 22, 521–531.PubMedCrossRefGoogle Scholar
  28. Cohen, L., Henzel, W. J., & Baeuerle, P. A. (1998). IKAP is a scaffold protein of the IkappaB kinase complex. Nature, 395, 292–296.PubMedCrossRefGoogle Scholar
  29. Cuajungco, M. P., Leyne, M., Mull, J., Gill, S. P., Lu, W., Zagzag, D., Axelrod, F. B., Maayan, C., Gusella, J. F., & Slaugenhaupt, S. A. (2003). Tissue-specific reduction in splicing efficiency of IKBKAP due to the major mutation associated with familial dysautonomia. American Journal of Human Genetics, 72, 749–758.PubMedCrossRefGoogle Scholar
  30. Dancis, J. (1968). Altered drug response in familial dysautonomia. Annals of the New York Academy of Sciences, 151, 876–879.PubMedGoogle Scholar
  31. Esberg, A., Huang, B., Johansson, M. J., & Bystrom, A. S. (2006). Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis. Molecular Cell, 24, 139–148.PubMedCrossRefGoogle Scholar
  32. Giarraffa, P., Berger, K. I., Chaikin, A. A., Axelrod, F. B., Davey, C., & Becker, B. (2005). Assessing efficacy of high-frequency chest wall oscillation in patients with familial dysautonomia. Chest, 128, 3377–3381.PubMedCrossRefGoogle Scholar
  33. Gitlow, S. E., Bertani, L. M., Wilk, E., Li, B. L., & Dziedzic, S. (1970). Excretion of catecholamine metabolites by children with familial dysautonomia. Pediatrics, 46, 513–522.PubMedGoogle Scholar
  34. Glickstein, J. S., Schwartzman, D., Friedman, D., Rutkowski, M., & Axelrod, F. B. (1993). Abnormalities of the corrected QT interval in familial dysautonomia: An indicator of autonomic dysfunction. Journal of Pediatrics, 122, 925–928.PubMedCrossRefGoogle Scholar
  35. Gold-von Simson, G., & Axelrod, F. B. (2006). Familial dysautonomia: Update and recent advances. Current Problems in Pediatric and Adolescent Health Care, 36, 218–237.PubMedCrossRefGoogle Scholar
  36. Grover-Johnson, N., & Pearson, J. (1976). Deficient vascular innervation in familial dysautonomia, an explanation for vasomotor instability. Neuropathology and Applied Neurobiology, 2, 217–224.CrossRefGoogle Scholar
  37. Gyepes, M. T., & Linde, L. M. (1968). Familial dysautonomia: The mechanism of aspiration. Radiology, 91, 471–475.Google Scholar
  38. Hasan, F., McCrodden, J. M., Kennedy, N. P., & Tipton, K. F. (1988). The involvement of intestinal monoamine oxidase in the transport and metabolism of tyramine. Journal of Neural Transmission, 26(Suppl), 1–9.PubMedGoogle Scholar
  39. Hawkes, N. A., Otero, G., Winkler, G. S., Marshall, N., Dahmus, M. E., Krappmann, D., Scheidereit, C., Thomas, C. L., Schiavo, G., Erdjument-Bromage, H., Tempst, P., & Svejstrup, J. Q. (2002). Purification and characterization of the human elongator complex. Journal of Biological Chemistry, 277, 3047–3052.PubMedCrossRefGoogle Scholar
  40. Hayek, S., Laplaza, F. J., Axelrod, F. B., & Burke, S. W. (2000). Spinal deformity in familial dysautonomia. Prevalence, and results of bracing. Journal of Bone and Joint Surgery, 82-A, 1558–1562.PubMedGoogle Scholar
  41. Hilz, M. J., Axelrod, F. B., Bickel, A., Stemper, B., Brys, M., Wendelschafer-Crabb, G., & Kennedy, W. R. (2004). Assessing function and pathology in familial dysautonomia: Assessment of temperature perception, sweating and cutaneous innervation. Brain, 127(Pt 9), 2090–2098.PubMedCrossRefGoogle Scholar
  42. Hilz, M. J., Stemper, B., Sauer, P., Haertl, U., Singer, W., & Axelrod, F. B. (1999). Cold face test demonstrates parasympathetic cardiac dysfunction in familial dysautonomia. American Journal of Physiology, 276, R1833–R1839.PubMedGoogle Scholar
  43. Holmberg, C., Katz, S., Lerdrup, M., Herdegen, T., Jaattela, M., Aronheim, A., & Kallunki, T. (2002). A novel specific role for I kappa B kinase complex-associated protein in cytosolic stress signaling. Journal of Biological Chemistry, 277, 31918–31928.PubMedCrossRefGoogle Scholar
  44. Horwitz, D., Lovenberg, W., Engelman, K., & Sjoerdsma, A. (1964). Monoamine oxidase inhibitors, tyramine, and cheese. JAMA, 188, 1108–1110.PubMedGoogle Scholar
  45. Huie, M. L., Tsujino, S., Sklower Brooks, S., Engel, A., Elias, E., Bonthron, D. T., Bessley, C., Shanske, S., DiMauro, S., Goto, Y. I., & Hirschhorn, R. (1998). Glycogen storage disease type II: Identification of four novel missense mutations (D645N, G648S, R672W, R672Q) and two insertions/deletions in the acid alpha-glucosidase locus of patients of differing phenotype. Biochemical and Biophysical Research Communications, 244, 921–927.PubMedCrossRefGoogle Scholar
  46. Ilett, K. F., George, C. F., & Davies, D. S. (1980). The effect of monoamine oxidase inhibitors on ‘first-pass’ metabolism of tyramine in dog intestine. Biochemical Pharmacology, 29, 2551–2556.PubMedCrossRefGoogle Scholar
  47. Johnston, J. P. (1968). Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochemical Pharmacology, 17, 1285–1297.PubMedCrossRefGoogle Scholar
  48. Klein C. J., & Dyck, P. J. (2005) Hereditary sensory and autonomic neuropathies. In P. J. Dyck & P. K. Thomas (Eds.), Peripheral neuropathy (pp. 1809–1844). Philadelphia: Elsevier Saunders.Google Scholar
  49. Knoll, J., & Magyar, K. (1972). Some puzzling pharmacological effects of monoamine oxidase inhibitors. Advances in Biochemical Psychopharmacology, 5, 393–408.PubMedGoogle Scholar
  50. Krausz, Y., Maayan, C., Faber, J., Marciano, R., Mogle, P., & Wynchank, S. (1994). Scintigraphic evaluation of esophageal transit and gastric emptying in familial dysautonomia. European Journal of Radiology, 18, 52–56.PubMedCrossRefGoogle Scholar
  51. Kure, S., Hou, D. C., Suzuki, Y., Yamagishi, A., Hiratsuka, M., Fukuda, T., Sugie, H., Kondo, N., Matsubara, Y., & Narisawa, K. (2000). Glycogen storage disease type Ib without neutropenia. Journal of Pediatrics, 137, 253–256.PubMedCrossRefGoogle Scholar
  52. Lehavi, O., Aizenstein, O., Bercovich, D., Pavzner, D., Shomrat, R., Orr-Urtreger, A., & Yaron, Y. (2003). Screening for familial dysautonomia in Israel: Evidence for higher carrier rate among Polish Ashkenazi Jews. Genetic Testing, 7, 139–142.PubMedCrossRefGoogle Scholar
  53. Leyne, M., Mull, J., Gill, S. P., Cuajungco, M. P., Oddoux, C., Blumenfeld, A., Maayan, C., Gusella, J. F., Axelrod, F. B., & Slaugenhaupt, S. A. (2003). Identification of the first non-Jewish mutation in familial Dysautonomia. American Journal of Medical Genetics, 118, 305–308.CrossRefGoogle Scholar
  54. Linde, L. M., & Westover, J. L. (1962). Esophageal and gastric abnormalities in dysautonomia. Pediatrics, 29, 303–306.PubMedGoogle Scholar
  55. Lippman, S. B., & Nash, K. (1990). Monoamine oxidase inhibitor update. Potential adverse food and drug interactions. Drug Safety, 5, 195–204.PubMedCrossRefGoogle Scholar
  56. Maayan, H. C. (2006). Respiratory aspects of Riley-Day Syndrome: Familial dysautonomia. Paediatric Respiratory Reviews, 7(Suppl 1), S258–S259.PubMedCrossRefGoogle Scholar
  57. Maayan, C., Kaplan, E., Shachar, S., Peleg, O., & Godfrey, S. (1987). Incidence of familial dysautonomia in Israel 1977–1981. Clinical Genetics, 32, 106–108.PubMedCrossRefGoogle Scholar
  58. Margulies, S. I., Brunt, P. W., Donner, M. W., & Silbiger, M. L. (1968). Familial dysautonomia. A cineradiographic study of the swallowing mechanism. Radiology, 90, 107–112.PubMedGoogle Scholar
  59. Mayer, S. E. (1980). Neurohumoral transmission and the autonomic nervous system, Chapter 4. In A. G. Gilman, L. S. Goodman, & A. Gilman (Eds.), The pharmacological basis of therapeutics (6th ed., p. 82). New York: The Macmillan Company.Google Scholar
  60. McCabe, B., & Tsuang, M. T. (1982). Dietary consideration in MAO inhibitor regimens. Journal of Clinical Psychiatry, 43, 178–181.PubMedGoogle Scholar
  61. Otero, G., Fellows, J., Li, Y., de Bizemont, T., Dirac, A. M., Gustafsson, C. M., Erdjument-Bromage, H., Tempst, P., & Svejstrup, J. Q. (1999). Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation. Molecular Cell, 3, 109–118.PubMedCrossRefGoogle Scholar
  62. Pearson, J., Axelrod, F., & Dancis, J. (1974). Trophic functions of the neuron. V. Familial dysautonomis. Current concepts of dysautonomia: Neuropathological defects. Annals of the New York Academy of Sciences, 228, 288–300.PubMedCrossRefGoogle Scholar
  63. Pearson, J., Dancis, J., Axelrod, F., & Grover, N. (1975). The sural nerve in familial dysautonomia. Journal of Neuropathology and Experimental Neurology, 34, 413–424.PubMedCrossRefGoogle Scholar
  64. Pearson, J., & Pytel, B. (1978a). Quantitative studies of ciliary and sphenopalatine ganglia in familial dysautonomia. Journal of the Neurological Sciences, 39, 123–130.PubMedCrossRefGoogle Scholar
  65. Pearson, J., & Pytel, B. A. (1978b). Quantitative studies of sympathetic ganglia and spinal cord intermedio-lateral gray columns in familial dysautonomia. Journal of the Neurological Sciences, 39, 47–59.PubMedCrossRefGoogle Scholar
  66. Pearson, J., Pytel, B. A., Grover-Johnson, N., Axelrod, F., & Dancis, J. (1978). Quantitative studies of dorsal root ganglia and neuropathologic observations on spinal cords in familial dysautonomia. Journal of the Neurological Sciences, 35, 77–92.PubMedCrossRefGoogle Scholar
  67. Rahl, P. B., Chen, C. Z., & Collins, R. N. (2005). Elp1p, the yeast homolog of the FD disease syndrome protein, negatively regulates exocytosis independently of transcriptional elongation. Molecular Cell, 17, 841–853.PubMedCrossRefGoogle Scholar
  68. Ravaris, C. L., Robinson, D. S., Nies, A., Ives, J. O., & Bartlett, D. (1978). Use of MAOI antidepressants. American Family Physician, 18, 105–111.PubMedGoogle Scholar
  69. Riley, C. M. (1974). Trophic functions of the neuron. V. Familial dysautonomia. Familial dysautonomia: Clinical and pathophysiological aspects. Annals of the New York Academy of Sciences, 228, 283–287.PubMedCrossRefGoogle Scholar
  70. Riley, C. M., Day, R. L., Greely, D., & Langford, W. S. (1949). Central autonomic dysfunction with defective lacrimation. Pediatrics, 3, 468–477.PubMedGoogle Scholar
  71. Rubin, B. Y., Kapas, L., & Anderson, S. L. (2007) Can the therapeutic efficacy of tocotrienols in neurodegenerative Familial Dysautonomia patients be measured clinically? Antioxidants & Redox Signaling, in press.Google Scholar
  72. Slaugenhaupt, S. A., Blumenfeld, A., Gill, S. P., Leyne, M., Mull, J., Cuajungco, M. P., Liebert, C. B., Chadwick, B., Idelson, M., Reznik, L., Robbins, C., Makalowska, I., Brownstein, M., Krappmann, D., Scheidereit, C., Maayan, C., Axelrod, F. B., & Gusella, J. F. (2001). Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. American Journal of Human Genetics, 68, 598–605.PubMedCrossRefGoogle Scholar
  73. Slaugenhaupt, S. A., Mull, J., Leyne, M., Cuajungco, M. P., Gill, S. P., Hims, M. M., Quintero, F., Axelrod, F. B., & Gusella, J. F. (2004). Rescue of a human mRNA splicing defect by the plant cytokinin kinetin. Human Molecular Genetics, 13, 429–436.PubMedCrossRefGoogle Scholar
  74. Smith, A. A., & Dancis, J. (1963). Response to intradermal histamine in familial dysautonomia–a diagnostic test. Journal of Pediatrics, 63, 889–894.PubMedCrossRefGoogle Scholar
  75. Smith, A. A., & Dancis, J. (1964) Exaggerated response to infused norepinephrine in familial dysautonomia. New England Journal of Medicine, 270, 704–707.PubMedCrossRefGoogle Scholar
  76. Smith, A. A., & Dancis, J. (1967). Catecholamine release in familial dysautonomia. New England Journal of Medicine, 277, 61–64.PubMedCrossRefGoogle Scholar
  77. Smith, A. A., Dancis, J., & Breinin, G. (1965b). Ocular responses to autonomic drugs in familial dysautonomia. Investigative Ophthalmology, 4, 358–361.PubMedGoogle Scholar
  78. Smith, A., Farbman, A., & Dancis, J. (1965). Absence of taste-bud papillae in familial dysautonomia. Science, 147, 1040–1041.PubMedCrossRefGoogle Scholar
  79. Smith, A. A., Hirsch, J. I., & Dancis, J. (1965a). Responses to infused methacholine in familial dysautonomia. Pediatrics, 36, 225–230.PubMedGoogle Scholar
  80. Smith, A. A., Taylor, T., & Wortis, S. B. (1963). Abnormal catechol amine metabolism in familial dysautonomia. New England Journal of Medicine, 268, 705–707.PubMedCrossRefGoogle Scholar
  81. Svejstrup, J. Q. (2007). Elongator complex: How many roles does it play? Current Opinion in Cell Biology, 19, 331–336.PubMedCrossRefGoogle Scholar
  82. Svenson, I. K., Ashley-Koch, A. E., Gaskell, P. C., Riney, T. J., Cumming, W. J., Kingston, H. M., Hogan, E. L., Boustany, R. M., Vance, J. M., Nance, M. A., Pericak-Vance, M. A., & Marchuk, D. A. (2001a). Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia. American Journal of Human Genetics, 68, 1077–1085.PubMedCrossRefGoogle Scholar
  83. Svenson, I. K., Ashley-Koch, A. E., Pericak-Vance, M. A., & Marchuk, D. A. (2001b). A second leaky splice-site mutation in the spastin gene. American Journal of Human Genetics, 69, 1407–1409.PubMedCrossRefGoogle Scholar
  84. Tollefson, G. D. (1983). Monoamine oxidase inhibitors: A review. Journal of Clinical Psychiatry, 44, 280–288.PubMedGoogle Scholar
  85. Walker, J. I., Davidson, J., & Zung, W. W. (1984). Patient compliance with MAO inhibitor therapy. Journal of Clinical Psychiatry, 45, 78–80.PubMedGoogle Scholar
  86. Winkler, G. S., Kristjuhan, A., Erdjument-Bromage, H., Tempst, P., & Svejstrup, J. Q. (2002). Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels in vivo. Proceedings of the National Academy of Sciences of the United States of America, 99, 3517–3522.PubMedCrossRefGoogle Scholar
  87. Wyatt, M. P., Barrack, R. L., Mubarak, S. J., Whitecloud, T. S., & Burke, S. W. (1986). Vibratory response in idiopathic scoliosis. Journal of Bone and Joint Surgery, 68, 714–718.Google Scholar
  88. Yekutiel, M., Robin, G. C., & Yarom, R. (1981). Proprioceptive function in children with adolescent idiopathic scoliosis. Spine, 6, 560–666.PubMedCrossRefGoogle Scholar
  89. Yoslow, W., Becker, M. H., Bartels, J., & Thompson, W. A. (1971). Orthopaedic defects in familial dysautonomia. A review of 65 cases. Journal of Bone and Joint Surgery. American Volume, 53, 1541–1550.Google Scholar
  90. Youdim, M. B., Heldman, E., Pollard, H. B., Fleming, P., & McHugh, E. (1986). Contrasting monoamine oxidase activity and tyramine induced catecholamine release in PC12 and chromaffin cells. Neuroscience, 19, 1311–1318.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  1. 1.Department of Biological Sciences, Laboratory for Familial Dysautonomia ResearchFordham UniversityBronxUSA

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