Solving the puzzle of spinal muscular atrophy: What are the missing pieces?

American Journal of Medical Genetics, Part A

Volumn 161, Issue 11, 2013, Pages 2836-2845

  Tiziano, Francesco Danilo ^a   Melki, Judith ^b   Simard, Louise R ^c  

^a CATHOLIC UNIVERSITY   (Italy)

^b Universite Paris Sud   (France)

^c UNIVERSITY OF MANITOBA   (Canada)

Author keywords

SMN; Spinal muscular atrophy

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; ARYLBUTYRIC ACID DERIVATIVE; HISTONE DEACETYLASE INHIBITOR; SURVIVAL MOTOR NEURON PROTEIN 1; SURVIVAL MOTOR NEURON PROTEIN 2; TRICHOSTATIN A; VALPROIC ACID; VIRUS VECTOR; VORINOSTAT;

AGE; ARTICLE; AUTONOMIC DYSFUNCTION; CELL VIABILITY; COMORBIDITY; DISEASE SEVERITY; DRUG DOSAGE FORM COMPARISON; GENE; GENE DELETION; GENE DOSAGE; GENE EXPRESSION; GENE MUTATION; GENE REPLACEMENT THERAPY; HEREDITARY SPINAL MUSCULAR ATROPHY; HUMAN; INTERMEDIATE HEREDITARY SPINAL MUSCULAR ATROPHY; KUGELBERG WELANDER DISEASE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; RNA SPLICING; SMN1 GENE; SMN2 GENE; SURVIVAL; UNSPECIFIED SIDE EFFECT; VIRAL GENE DELIVERY SYSTEM; WERDNIG HOFFMANN DISEASE;

SMN; SPINAL MUSCULAR ATROPHY;

ANIMALS; HISTONE DEACETYLASE INHIBITORS; HUMANS; MUSCULAR ATROPHY, SPINAL; SURVIVAL OF MOTOR NEURON 1 PROTEIN; SURVIVAL OF MOTOR NEURON 2 PROTEIN; TREATMENT OUTCOME;

EID: 84886237326     PISSN: 15524825     EISSN: 15524833     Source Type: Journal    
DOI: 10.1002/ajmg.a.36251     Document Type: Article

References (137)

1. Alías L, Bernal S, Fuentes-Prior P, Barceló MJ, Also E, Martínez-Hernández R, Rodríguez-Alvarez FJ, Martín Y, Aller E, Grau E, Peciña A, Antiñolo G, Galán E, Rosa AL, Fernández-Burriel M, Borrego S, Millán JM, Hernández-Chico C, Baiget M, Tizzano EF. 2009. Mutation update of spinal muscular atrophy in Spain: Molecular characterization of 745 unrelated patients and identification of four novel mutations in the SMN1 gene. Hum Genet 125:29-39.
2. Anderton RS, Meloni BP, Mastaglia FL, Boulos S. 2013. Spinal muscular atrophy and the antiapoptotic role of survival of motor neuron (SMN) protein. Mol Neurobiol 47:821-832.
3. Andreassi C, Angelozzi C, Tiziano FD, Vitali T, De Vincenzi E, Boninsegna A, Villanova M, Bertini E, Pini A, Neri G, Brahe C. 2004. Phenylbutyrate increases SMN expression in vitro: Relevance for treatment of spinal muscular atrophy, Eur J Hum Genet 12:59-65.
4. Avila AM, Burnett BG, Taye AA, Gabanella F, Knight MA, Hartenstein P, Cizman Z, Di Prospero NA, Pellizzoni L, Fischbeck KH, Sumner CJ. 2007. Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy. J Clin Invest 3:659-671.
5. Baccon J, Pellizzoni L, Rappsilber J, Mann M, Dreyfuss G. 2002. Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex. J Biol Chem 277:31957-31962.
6. Bach JR. 2007. Medical considerations of long-term survival of Werdnig-Hoffmann disease. Am J Phys Med Rehabil 86:349-355.
7. Baron-Delage S, Abadie A, Echaniz-Laguna A, Melki J, Beretta L. 2000. Interferons and IRF-1 induce expression of the survival motor neuron (SMN) genes. Mol Med 6:957-968.
8. Battaglia G, Princivalle A, Forti F, Lizier C, Zeviani M. 1997. Expression of the SMN gene, the spinal muscular atrophy determining gene, in the mammalian central nervous system. Hum Mol Genet 6:1961-1971.
9. Bäumer D, Lee S, Nicholson G, Davies JL, Parkinson NJ, Murray LM, Gillingwater TH, Ansorge O, Davies KE, Talbot K. 2009. Alternative splicing events are a late feature of pathology in a mouse model of spinal muscular atrophy. PLoS Genet 5:e1000773.
10. Béchade C, Rostaing P, Cisterni C, Kalisch R, La Bella V, Pettmann B, Triller A. 1999. Subcellular distribution of survival motor neuron (SMN) protein: Possible involvement in nucleocytoplasmic and dendritic transport. Eur J Neurosci 11:293-304.
11. Boda B, Mas C, Giudicelli C, Nepote V, Guimiot F, Levacher B, Zvara A, Santha M, LeGall I, Simonneau M. 2004. Survival motor neuron SMN1 and SMN2 gene promoters: Identical sequences and differential expression in neurons and non-neuronal cells. Eur J Hum Genet 12:729-737.
12. Bowerman M, Shafey D, Kothary R. 2007. Smn depletion alters profilin II expression and leads to upregulation of the RhoA/ROCK pathway and defects in neuronal integrity. J Mol Neurosci 32:120-131.
13. Bowerman M, Anderson CL, Beauvais A, Boyl PP, Witke W, Kothary R. 2009. SMN, profilin IIa and plastin 3: A link between the deregulation of actin dynamics and SMA pathogenesis. Mol Cell Neurosci 42:66-74.
14. Bowerman M, Beauvais A, Anderson CL, Kothary R. 2010. Rho-kinase inactivation prolongs survival of an intermediate SMA mouse model. Hum Mol Genet 19:1468-1478.
15. Bowerman M, Murray LM, Beauvais A, Pinheiro B, Kothary R. 2012. A critical SMN threshold in mice dictates onset of an intermediate spinal muscular atrophy phenotype associated with a distinct neuromuscular junction pathology. Neuromuscul Disord 22:263-276.
16. Brahe C, Vitali T, Tiziano FD, Angelozzi C, Pinto AM, Borgo F, Moscato U, Bertini E, Mercuri E, Neri G. 2005. Phenylbutyrate increases SMN gene expression in spinal muscular atrophy patients. Eur J Hum Genet 13:256-259.
17. Brichta L, Hoffman Y, Hahnen E, Siebzehnrubl FA, Raschke H, Blumcke I, Eyupoglu IY, Wirth B. 2003. Valproic acid increases the SMN2 protein level; a well known drug as a potential therapy for spinal muscular atrophy. Hum Mol Genet 12:2481-2489.
18. Broccolini A, Engel WK, Askanas V. 1999. Localization of survival motor neuron protein in human apoptotic-like and regenerating muscle fibers, and neuromuscular junctions. Neuroreport 10:1637-1641.
19. Burghes AH. 1997. When is a deletion not a deletion? When it is converted. Am J Hum Genet 61:9-15.
20. Burghes AH, Beattie CE. 2009. Spinal muscular atrophy: Why do low levels of survival motor neuron protein make motor neurons sick? Nat Rev Neurosci 10:597-609.
21. Burlet P, Huber C, Bertrandy S, Ludosky MA, Zwaenepoel I, Clermont O, Roume J, Delezoide AL, Cartaud J, Munnich A, Lefebvre S. 1998. The distribution of SMN protein complex in human fetal tissues and its alteration in spinal muscular atrophy. Hum Mol Genet 7:1927-1933.
22. Carissimi C, Saieva L, Baccon J. 2006. Gemin8 is a novel component of the survival motor neuron complex and functions in small nuclear ribonucleoprotein assembly. J Biol Chem 281:8126-8134.
23. Cartegni L, Krainer AR. 2002. Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1. Nat Genet 30:377-384.
24. Chang JG, Hsieh-Li HM, Jong YJ, Wang NM, Tsai CH, Li H. 2001. Treatment of spinal muscular atrophy by sodium butyrate. Proc Nat Acad Sci USA 98:9808-9813.
25. Charroux B, Pellizzoni L, Perkinson RA, Shevchenko A, Mann M, Dreyfuss G. 1999. Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems. J Cell Biol 147:1181-1194.
26. Charroux B, Pellizzoni L, Perkinson RA. 2000. Gemin4: A novel component of the SMN complex that is found in both gems and nucleoli. J Cell Biol 148:1177-1186.
27. Chen HH, Chang JG, Lu RM, Peng TY, Tarn WY. 2008. The RNA binding protein hnRNP Q modulates the utilization of exon 7 in the survival motor neuron 2 (SMN2) gene. Mol Cell Biol 28:6929-6938.
28. Cho S, Dreyfuss G. 2010. A degron created by SMN2 exon 7 skipping is a principal contributor to spinal muscular atrophy severity. Genes Dev 24:438-442.
29. Cifuentes Diaz C, Nicole S, Velasco ME, Borra-Cebrian C, Panozzo C, Frugier T, Millet G, Roblot N, Joshi V, Melki J. 2002. Neurofilament accumulation at the motor endplate and lack of axonal sprouting in a spinal muscular atrophy mouse model. Hum Mol Genet 11:1439-1447.
30. Cisterni C, Kallenbach S, Jordier F, Bagnis C, Pettmann B. 2001. Death of motoneurons induced by trophic deprivation or by excitotoxicity is not prevented by overexpression of SMN, Neurobiol Dis 8:240-251.
31. Coovert DD, Le TT McAndrew PE, Strasswimmer J, Crawford TO, Mendell JR, Coulson SE, Androphy EJ, Prior TW, Burghes AHM. 1997. The survival motor neuron protein in spinal muscular atrophy. Hum Mol Genet 6:1205-1214.
32. Courseaux A, Richard F, Grosgeorge J, Ortola C, Viale A, Turc-Carel C, Dutrillaux B, Gaudray P, Nahon JL. 2003. Segmental duplications in euchromatic regions of human chromosome 5: A source of evolutionary instability and transcriptional innovation. Genome Res 13:369-381.
33. Crawford TO, Pardo CA. 1996. The neurobiology of childhood spinal muscular atrophy. Neurobiol Dis 3:97-110.
34. Crawford TO, Paushkin SV, Kobayashi DT, Forrest SJ, Joyce CL, Finkel RS, Kaufmann P, Swoboda KJ, Tiziano D, Lomastro R, Li RH, Trachtenberg FL, Plasterer T, Chen KS, Pilot Study of Biomarkers for Spinal Muscular Atrophy Trial Group. 2012. Evaluation of SMN protein, transcript, and copy number in the biomarkers for spinal muscular atrophy (BforSMA) clinical study. PLoS ONE 7:e33572.
35. Darbar IA, Plaggert PG, Resende MB, Zanoteli E, Reed UC. 2011. Evaluation of muscle strength and motor abilities in children with type II and III spinal muscle atrophy treated with valproic acid. BMC Neurol 11:36.
36. DiDonato CJ, Ingraham SE, Mendell JR, Prior TW, Lenard S, Moxley RT III, Florence J, Burghes AH. 1997. Deletion and conversion in spinal muscular atrophy patients: Is there a relationship to severity? Ann Neurol 41:230-237.
37. Dominguez E, Marais T, Chatauret N, Benkhelifa-Ziyyat S, Duque S, Ravassard P, Carcenac R, Astord S, Pereira de Moura A, Voit T, Barkats M. 2011. Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA mice. Hum Mol Genet 20:681-693.
38. Dubowitz V. 1995. Chaos in the classification of SMA: A possible resolution. Neuromuscul Disord 5:3-5.
39. Echaniz-Laguna A, Miniou P, Bartholdi D, Melki J. 1999. The promoters of the survival motor neuron gene (SMN) and its copy (SMNc) share common regulatory elements. Am J Hum Genet 64:1365-1370.
40. Fallini C, Bassell GJ, Rossoll W. 2012. Spinal muscular atrophy: The role of SMN in axonal mRNA regulation. Brain Res 1462:81-92.
41. Fan L, Simard LR. 2002. Survival motor neuron (SMN) protein: Role in neurite outgrowth and neuromuscular maturation during neuronal differentiation and development. Hum Mol Genet 11:1605-1614.
42. Feldkotter M, Schwarzer V, Wirth R, Wienker TI, Wirth B. 2002. Quantitative analysis of SMN1 and SMN2 based on real time lightcycler PCR: Fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet 70:358-368.
43. Fidziańska A, Rafalowska J. 2002. Motoneuron death in normal and spinal muscular atrophy-affected human fetuses. Acta Neuropathol 104:363-368.
44. Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, Kaspar BK. 2010. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol 28:271-274.
45. Francis JW, Sandrock AW, Bhide PG, Vonsattel JP, Brown RH Jr. 1998. Heterogeneity of subcellular localization and electrophoretic mobility of survival motor neuron (SMN) protein in mammalian neural cells and tissues. Proc Natl Acad Sci USA 95:6492-6497.
46. Gabanella F, Carissimi C, Usiello A, Pellizzoni L. 2005. The activity of the spinal muscular atrophy protein is regulated during development and cellular differentiation. Hum Mol Genet 23:3629-3642.
47. Germain-Desprez D, Brun T, Rochette C, Semionov A, Rouget R, Simard LR. 2001. The SMN genes are subject to transcriptional regulation during cellular differentiation. Gene 279:109-117.
48. Giavazzi A, Setola V, Simonati A, Battaglia G. 2006. Neuronal-specific roles of the survival motor neuron protein: Evidence from survival motor neuron expression patterns in the developing human central nervous system. J Neuropathol Exp Neurol 65:267-277.
49. Giesemann T, Rathke-Hartlieb S, Rothkegel M, Bartsch JW, Buchmeier S, Jockusch BM, Jockusch H. 1999. A role for polyproline motifs in the spinal muscular atrophy protein SMN. Profilins bind to and colocalize with SMN in nuclear gems. J Biol Chem 274:37908-37914.
50. Gladman JT, Chandler DS. 2009. Intron 7 conserved sequence elements regulate the splicing of the SMN genes. Hum Genet 126:833-841.
51. Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G. 2002. Gemin5, a novel WD repeat protein component of the SMN complex that binds SM proteins. J Biol Chem 277:5631-5636.
52. Hachiya Y, Arai H, Hayashi M, Kumada S, Furushima W, Ohtsuka E, Ito Y, Uchiyama A, Kurata K. 2005. Autonomic dysfunction in cases of spinal muscular atrophy type 1 with long survival. Brain Dev 27:574-578.
53. Hahnen E, Schönling J, Rudnik-Schöneborn S, Zerres K, Wirth B. 1996. Hybrid survival motor neuron genes in patients with autosomal recessive spinal muscular atrophy: New insights into molecular mechanisms responsible for the disease. Am J Hum Genet 59:1057-1065.
54. Hahnen E, Eyüpoglu IY, Brichta L, Haastert K, Tränkle C, Siebzehnrübl FA, Riessland M, Hölker I, Claus P, Romstöck J, Buslei R, Wirth B, Blümcke I. 2006. In vitro and ex vivo evaluation of second-generation histone deacetylase inhibitors for the treatment of spinal muscular atrophy. J Neurochem 98:193-202.
55. Hamilton G, Gillingwater TH. 2013. Spinal muscular atrophy: Going beyond the motor neuron. Trends Mol Med 19:40-50.
56. Hauke J, Riessland M, Lunke S, Eyüpoglu IY, Blümcke I, El-Osta A, Wirth B, Hahnen E. 2009. Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition. Hum Mol Genet 18:304-317.
57. Hofmann Y, Wirth B. 2002. HnRNP-G promotes exon 7 inclusion of survival motor neuron (SMN) via direct interaction with Htra2-beta1. Hum Mol Genet 11:2037-2049.
58. Hua Y, Vickers TA, Baker BF, Bennett CF, Krainer AR. 2007. Enhancement of SMN2 exon 7 inclusion by antisense oligonucleotides targeting the exon. PLoS Biol 5:e73.
59. Hua Y, Vickers TA, Okunola HL, Bennett CF, Krainer AR. 2008. Antisense masking of an hnRNP A1/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice. Am J Hum Genet 82:834-848.
60. Hua Y, Sahashi K, Hung G, Rigo F, Passini MA, Bennett CF, Krainer AR. 2010. Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev 24:1634-1644.
61. Hua Y, Sahashi K, Rigo F, Hung G, Horev G, Bennett CF, Krainer AR. 2011. Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model. Nature 478:123-126.
62. Ibrahim F, Nakaya T, Mourelatos Z. 2012. RNA dysregulation in diseases of motor neurons. Annu Rev Pathol 7:323-352.
63. Ito Y, Shibata N, Saito K, Kobayashi M, Osawa M. 2011. New insights into the pathogenesis of spinal muscular atrophy. Brain Dev 33:321-331.
64. Jablonka S, Wiese S, Sendtner M. 2004. Axonal defects in mouse models of motoneuron disease. J Neurobiol 58:272-286.
65. Kashima T, Manley JL. 2003. A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy, Nat Genet 34:460-463.
66. Kernochan LE, Russo ML, Woodling NS, Huynh TN, Avila AM, Fischbeck KH, Sumner CJ. 2005. The role of histone acetylation in SMN gene expression. Hum Mol Genet 14:1171-1182.
67. Kissel JT, Scott CB, Reyna SP, Crawford TO, Simard LR, Krosschell KJ, Acsadi G, Elsheik B, Schroth MK, D'Anjou G, LaSalle B, Prior TW, Sorenson S, Maczulski JA, Bromberg MB, Chan GM, Swoboda KJ, Project Cure Spinal Muscular Atrophy Investigators' Network. 2011. SMA Carnival Trial Part II: A prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy. PLoS ONE 6:e21296.
68. Kissel JT, Elsheikh B, King WM, Freimer M, Scott CB, Kolb SJ, Reyna SP, Crawford TO, Simard LR, Krosschell KJ, Acsadi G, Schroth MK, D'Anjou G, Lasalle B, Prior TW, Sorenson S, Maczulski JA, Swoboda KJ. for the Project Cure Spinal Muscular Atrophy Investigators Network. 2013. SMA valiant trial: A prospective, double-blind, placebo-controlled trial of valproic acid in ambulatory adults with spinal muscular atrophy. Muscle Nerve epub ahead of print.
69. Kobayashi DT, Shi J, Stephen L, Ballard KL, Dewey R, Mapes J, Chung B, McCarthy K, Swoboda KJ, Crawford TO, Li R, Plasterer T, Joyce C, Biomarkers for Spinal Muscular Atrophy Study Group, Chung WK, Kaufmann P, Darras BT, Finkel RS, Sproule DM, Martens WB, McDermott MP, De Vivo DC, Pediatric Neuromuscular Clinical Research Network, Walker MG, Chen KS, 2013. SMA-MAP: A plasma protein panel for spinal muscular atrophy. PLoS ONE 8:e60113.
70. La Bella V, Cisterni C, Salaün D, Pettmann B. 1998. Survival motor neuron (SMN) protein in rat is expressed as different molecular forms and is developmentally regulated. Eur J Neurosci 10:2913-2923.
71. La Bella V, Kallenbach S, Pettmann B. 2000. Expression and subcellular localization of two isoforms of the survival motor neuron protein in different cell types. J Neurosci Res 62:346-356.
72. Le TT, Pham LT, Butchbach ME. 2005. SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN, Hum Mol Genet 14:845-857.
73. Le TT, McGovern VL, Alwine IE, Wang IX, Massoni-Laporte A, Rich MM, Burghes AH. 2011. Temporal requirement for high SMN expression in SMA mice. Hum Mol Genet 20:3578-3591.
74. Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, Le Paslier D, Frézal J, Cohen D, Weissenbach J, Munnich A, Melki J. 1995. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80:155-165.
75. Lefebvre S, Burlet P, Liu Q, Bertrandy S, Clermont O, Munnich A, Dreyfuss G, Melki J. 1997. Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet 3:265-269.
76. Liu Q, Dreyfuss G. 1996. A novel nuclear structure containing the survival of motor neurons protein. Embo J 15:3555-3565.
77. Lorson CL, Strasswimmer J, Yao JM, Baleja JD, Hahnen E, Wirth B, Le T, Burghes AH, Androphy EJ. 1998. SMN oligomerization defect correlates with spinal muscular atrophy severity. Nat Genet 19:63-66.
78. Lorson CL, Hahnen E, Androphy EJ, Wirth B. 1999. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci USA 96:6307-6311.
79. Lotti F, Imlach WL, Saieva L, Beck ES, Hao le T, Li DK, Jiao W, Mentis GZ, Beattie CE, McCabe BD, Pellizzoni L. 2012. An SMN-dependent U12 splicing event essential for motor circuit function. Cell 151:440-454.
80. Lutz CM, Kariya S, Patruni S, Osborne MA, Liu D, Henderson CE, Li DK, Pellizzoni L, Rojas J, Valenzuela DM, Murphy AJ, Winberg ML, Monani UR. 2011. Postsymptomatic restoration of SMN rescues the disease phenotype in a mouse model of severe spinal muscular atrophy. J Clin Invest 121:3029-3041.
81. Majumder S, Varadharaj S, Ghoshal K, Monani U, Burghes AH, Jacob ST. 2004. Identification of a novel cyclic AMP-response element (CRE-II) and the role of CREB-1 in the cAMP-induced expression of the survival motor neuron (SMN) gene. J Biol Chem 279:14803-14811.
82. Mercuri E, Bertini E, Messina S, Pelliccioni M, D'Amico A, Colitto F, Mirabella M, Tiziano FD, Vitali T, Angelozzi C, Kinali M, Main M, Brahe C. 2004. Pilot trial of phenylbutyrate in spinal muscular atrophy. Neuromuscul Disord 14:130-135.
83. Mercuri E, Bertini E, Messina S, Solari A, D'Amico A, Angelozzi C, Battini R, Berardinelli A, Boffi P, Bruno C, Cini C, Colitto F, Kinali M, Minetti C, Mongini T, Morandi L, Neri G, Orcesi S, Pane M, Pelliccioni M, Pini A, Tiziano FD, Villanova M, Vita G, Brahe C. 2007. Randomized, double-blind, placebo-controlled trial of phenylbutyrate in spinal muscular atrophy. Neurology 68:51-55.
84. Mercuri E, Bertini E, Iannaccone ST. 2012. Childhood spinal muscular atrophy: Controversies and challenges. Lancet Neurol 11:443-452.
85. Mezzina M, Merten OW. 2011. Adeno-associated viruses. Methods Mol Biol 737:211-234.
86. Monani UR, Lorson CL, Parsons DW, Prior TW, Androphy EJ, Burghes AHM, McPherson JD. 1999. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2, Hum Mol Genet 8:1177-1183.
87. Monani UR, Sendtner M, Coovert DD. 2000. The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in SMN(-/-) mice and results in a mouse with spinal muscular atrophy. Hum Mol Genet 9:333-339.
88. Narvel HL, Kong L, Burnett BG, Choe DW, Bosch-Marcé M, Taye AA, Eckhaus MA, Sumner CJ. 2008. Sustained improvement of spinal muscular atrophy mice treated with trichostatin A plus nutrition. Ann Neurol 64:465-470.
89. Pagliardini S, Giavazzi A, Setola V, Lizier C, Di Luca M, DeBiasi S, Battaglia G. 2000. Subcellular localization and axonal transport of the survival motor neuron (SMN) protein in the developing rat spinal cord. Hum Mol Genet 9:47-56.
90. Passini MA, Bu J, Roskelley EM, Richards AM, Sardi SP, O'Riordan CR, Klinger KW, Shihabuddin LS, Cheng SH. 2010. CNS-targeted gene therapy improves survival and motor function in a mouse model of spinal muscular atrophy. J Clin Invest 120:1253-1264.
91. Passini MA, Bu J, Richards AM, Kinnecom C, Sardi SP, Stanek LM, Hua Y, Rigo F, Matson J, Hung G, Kaye EM, Shihabuddin LS, Krainer AR, Bennett CF, Cheng SH. 2011. Antisense oligonucleotides delivered to the mouse CNS ameliorate symptoms of severe spinal muscular atrophy. Sci Transl Med 3:72ra18.
92. Pellizzoni L, Baccon J, Rappsilber J, Mann M, Dreyfuss G. 2002. Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component. J Biol Chem 277:7540-7545.
93. Piepers S, Cobben JM, Sodaar P, Jansen MD, Wadman RI, Meester-Delver A, Poll-The BT, Lemmink HH, Wokke JH, van der Pol WL, van den Berg LH. 2011. Quantification of SMN protein in leucocytes from spinal muscular atrophy patients: Effects of treatment with valproic acid. J Neurol Neurosurg Psychiatry 82:850-852.
94. Porensky PN, Burghes AH. 2013. Antisense oligonucleotides for the treatment of spinal muscular atrophy. Hum Genet Ther 24:489-498.
95. Prior TW, Snyder PJ, Rink BD, Pearl DK, Pyatt RE, Mihal DC, Conlan T, Schmalz B, Montgomery L, Ziegler K, Noonan C, Hashimoto S, Garner S. 2010. Newborn and carrier screening for spinal muscular atrophy. Am J Med Genet A 152A:1608-1616.
96. Prior TW. 2010. Spinal muscular atrophy: A time for screening. Curr Opin Pediatr 22:696-702.
97. Pruss RM. 2011. Developments in the discovery of drugs for spinal muscular atrophy: Successful beginnings and future prospects. Expert Opin Drug Discov 6:827-837.
98. Riessland M, Ackermann B, Förster A, Jakubik M, Hauke J, Garbes L, Fritzsche I, Mende Y, Blumcke I, Hahnen E, Wirth B. 2010. SAHA ameliorates the SMA phenotype in two mouse models for spinal muscular atrophy. Hum Mol Genet 19:1492-1506.
99. Rochette CF, Gilbert N, Simard LR. 2001. SMN gene duplication and the emergence of the SMN2 gene occurred in distinct hominids: SMN2 is unique to Homo sapiens. Hum Genet 108:255-266.
100. Rossoll W, Kroning AK, Ohndorf UM, Steegborn C, Jablonka S, Sendtner M. 2002. Specific interaction of SMN, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: A role for Smn in RNA processing in motor axons? Hum Mol Genet 11:93-105.
101. Rossoll W, Jablonka S, Andreassi C, Kröning AK, Karle K, Monani UR, Sendtner M. 2003. Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of β-actin mRNA in growth cones of motoneurons. J Cell Biol 163:801-812.
102. Rouget R, Vigneault F, Codio C, Rochette C, Paradis I, Drouin R, Simard LR. 2005. Characterization of the survival motor neuron (SMN) promoter provides evidence for complex combinatorial regulation in undifferentiated and differentiated P19 cells. Biochem J 385:433-443.
103. Sanchez G, Dury AY, Murray LM, Biondi O, Tadesse H, El Fatimy R, Kothary R, Charbonnier F, Khandjian EW, Côté J. 2013. A novel function for the survival motoneuron protein as a translational regulator. Hum Mol Genet 22:668-684.
104. Sharma A, Lambrechts A, Hao le T, Le TT, Sewry CA, Ampe C, Burghes AH, Morris GE. 2005. A role for complexes of survival of motor neurons (SMN) protein with gemins and profilin in neurite-like cytoplasmic extensions of cultured nerve cells. Exp Cell Res 309:185-197.
105. Singh NK, Singh NN, Androphy EJ, Singh RN. 2006. Splicing of a critical exon of human survival motor neuron is regulated by a unique silencer element located in the last intron. Mol Cell Biol 26:1333-1346.
106. Singh NN, Singh RN, Androphy EJ. 2007. Modulating role of RNA structure in alternative splicing of a critical exon in the spinal muscular atrophy genes. Nucleic Acids Res 35:371-389.
107. Soler-Botija C, Ferrer I, Gich I, Baiget M, Tizzano EF. 2002. Neuronal death is enhanced and begins during foetal development in type I spinal muscular atrophy spinal cord. Brain 125:1624-1634.
108. Soler-Botija C, Cuscó I, Caselles L, López E, Baiget M, Tizzano EF. 2005. Implication of fetal SMN2 expression in type I SMA pathogenesis: Protection or pathological gain of function? J Neuropathol Exp Neurol 64:215-223.
109. Sumner CJ, Huynh TN, Markowitz JA, Perhac JS, Hill B, Coovert DD, Schussler K, Chen X, Jarecki J, Burghes AH, Taylor JP, Fischbeck KH. 2003. Valproic acid increases SMN levels in spinal muscular atrophy patient cells. Ann Neurol 54:647-654.
110. Sumner CJ, Kolb SJ, Harmison GG, Jeffries NO, Schadt K, Finkel RS, Dreyfuss G, Fischbeck KH. 2006. SMN mRNA and protein levels in peripheral blood: Biomarkers for SMA clinical trials. Neurology 66:1067-1073.
111. Swoboda KJ, Prior TW, Scott CB, McNaught TP, Wride MC, Reyna SP, Bromberg MB. 2005. Natural history of denervation in SMA: Relation to age, SMN2 copy number, and function. Ann Neurol 57:704-712.
112. Swoboda KJ, Scott CB, Reyna SP, Prior TW, LaSalle B, Sorenson SL, Wood J, Acsadi G, Crawford TO, Kissel JT, Krosschell KJ, D'Anjou G, Bromberg MB, Schroth MK, Chan GM, Elsheikh B, Simard LR. 2009. Phase II open label study of valproic acid in spinal muscular atrophy. PLoS ONE 4:e5268.
113. Swoboda KJ, Scott CB, Crawford TO, Simard LR, Reyna SP, Krosschell KJ, Acsadi G, Elsheik B, Schroth MK, D'Anjou G, LaSalle B, Prior TW, Sorenson SL, Maczulski JA, Bromberg MB, Chan GM, Kissel JT. 2010. Project Cure Spinal Muscular Atrophy Investigators Network. SMA CARNI-VAL trial part I: Double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy. PLoS ONE 5:e12140.
114. Swoboda KJ. 2010. Seize the day: Newborn screening for SMA. Am J Med Genet A 152A:1605-1607.
115. Tiziano FD, Bertini E, Messina S, Angelozzi C, Pane M, D'Amico A, Alfieri P, Fiori S, Battini R, Berardinelli A, Boffi P, Bruno C, Cini C, Minetti C, Mongini T, Morandi L, Orcesi S, Pelliccioni M, Pini A, Villanova M, Vita G, Locatelli M, Mercuri E, Brahe C. 2007. The Hammersmith functional score correlates with the SMN2 copy number: A multicentric study. Neuromuscul Disord 17:400-403.
116. Tiziano FD, Pinto AM, Fiori S, Lomastro R, Messina S, Bruno C, Pini A, Pane M, D'Amico A, Ghezzo A, Bertini E, Mercuri E, Neri G, Brahe C. 2010a. SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR. Eur J Hum Gen 18:52-58.
117. Tiziano FD, Lomastro R, Pinto AM, Messina S, D'Amico A, Fiori S, Angelozzi C, Pane M, Mercuri E, Bertini E, Neri G, Brahe C. 2010b. Salbutamol increases survival motor neuron (SMN) transcript levels in leucocytes of spinal muscular atrophy (SMA) patients: Relevance for clinical trial design. J Med Genet 47:856-858.
118. Tiziano FD, Lomastro R, Di Pietro L, Pasanisi MB, Fiori S, Angelozzi C, Abiusi E, Angelini C, Sorarù G, Gaiani A, Mongini T, Vercelli L, Vasco G, Vita G, Vita GL, Messina S, Politano L, Passamano L, Di Gregorio G, Montomoli C, Orsi C, Campanella A, Mantegazza R, Morandi L. 2013. Clinical and molecular cross-sectional study of a cohort of adult type III spinal muscular atrophy patients: Clues from a biomarker study. Eur J Hum Genet 21:630-636.
119. Tizzano EF, Cabot C, Baiget M. 1998. Cell-specific survival motor neuron gene expression during human development of the central nervous system: Implications for the pathogenesis of spinal muscular atrophy. Am J Pathol 153:355-361.
120. Treleaven CM, Tamsett TJ, Bu J, Fidler JA, Sardi SP, Hurlbut GD, Woodworth LA, Cheng SH, Passini MA, Shihabuddin LS, Dodge JC. 2012. Gene transfer to the CNS is efficacious in immune-primed mice harboring physiologically relevant titers of anti-AAV antibodies. Mol Ther 20:1713-1723.
121. Tsai LK, Yang CC, Hwu WL, Li H. 2007. Valproic acid treatment in six patients with spinal muscular atrophy. Eur J Neurol 14:e8-e9.
122. Tsai LK. 2012. Therapy development for spinal muscular atrophy in SMN independent targets. Neural Plast 2012:456478.
123. Valori CF, Ning K, Wyles M, Mead RJ, Grierson AJ, Shaw PJ, Azzouz M. 2010. Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy, Sci Transl Med 2:35-42.
124. van der Steege G, Grootscholten PM, Cobben JM, Zappata S, Scheffer H, den Dunnen JT, van Ommen GJ, Brahe C, Buys CH. 1996. Apparent gene conversions involving the SMN gene in the region of the spinal muscular atrophy locus on chromosome 5. Am J Hum Genet 59:834-838.
125. Van Meerbeke JP, Sumner CJ. 2011. Progress and promise: The current status of spinal muscular atrophy therapeutics. Discov Med 12:291-305.
126. Velasco E, Valero C, Valero A, Moreno F, Hernández-Chico C. 1996. Molecular analysis of the SMN and NAIP genes in Spanish spinal muscular atrophy (SMA) families and correlation between number of copies of cBCD541 and SMA phenotype. Hum Mol Genet 5:257-263.
127. Vitali T, Sossi V, Tiziano F, Zappata S, Giuli A, Paravatou-Petsotas Neri G, Brahe C. 1999. Detection of the survival motor neuron (SMN) genes by FISH: Further evidence for a role for SMN2 in the modulation of disease severity in SMA patients, Hum Mol Genet 8:2525-2532.
128. Vitte J, Fassier C, Tiziano FD, Dalard C, Soave S, Roblot N, Brahe C, Saugier-Veber P, Bonnefont JP, Melki J. 2007. Refined characterization of the expression and stability of the SMN gene products. Am J Pathol 171:1269-1280.
129. Wen HL, Lin YT, Ting CH, Lin-Chao S, Li H, Hsieh-Li HM. 2010. Stathmin, a microtubule-destabilizing protein, is dysregulated in spinal muscular atrophy. Hum Mol Genet 19:1766-1778.
130. Williams BY, Vinnakota S, Sawyer CA, Waldrep JC, Hamilton SL, Sarkar HK. 1999. Differential subcellular localization of the survival motor neuron protein in spinal cord and skeletal muscle. Biochem Biophys Res Commun 254:10-14.
131. Williams JH, Jayaraman B, Swoboda KJ, Barrett JS. 2012. Population pharmacokinetics of valproic acid in pediatric patients with epilepsy: Considerations for dosing spinal muscular atrophy patients. J Clin Pharmacol 52:1676-1688.
132. Wirth B. 2000. An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Hum Mutat 15:228-237.
133. Workman E, Kolb SJ, Battle DJ. 2012. Spliceosomal small nuclear ribonucleoprotein biogenesis defects and motor neuron selectivity in spinal muscular atrophy. Brain Res 1462:93-99.
134. Zhang HL, Pan F, Hong D, Shenoy SM, Singer RH, Bassell GJ. 2003. Active transport of the survival motor neuron protein and the role of exon-7 in cytoplasmic localization. J Neurosci 23:6627-6637.
135. Zhang H, Xing L, Rossoll W, Wichterle H, Singer RH, Bassell GJ. 2006. Multiprotein complexes of the survival of motor neuron protein SMN with Gemins traffic to neuronal processes and growth cones of motor neurons. J Neurosci 26:8622-8632.
136. Zhang Z, Lotti F, Dittmar K, Younis I, Wan L, Kasim M, Dreyfuss G. 2008. SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing. Cell 133:585-600.
137. Zong Y, Jin R. 2013. Structural mechanisms of the agrin-LRP4-MuSK signaling pathway in neuromuscular junction differentiation. Cell Mol Life Sci 70:3077-3088.