Synaptic signaling and aberrant RNA splicing in autism spectrum disorders

Frontiers in Synaptic Neuroscience

Volumn , Issue JAN, 2011, Pages

  Smith, Ryan M ^a   Sadee, Wolfgang ^a  

^a OHIO STATE UNIVERSITY   (United States)

Author keywords

Alternative RNA splicing; Autism spectrum disorder; Cellular adhesion molecules; Gene expression; Neural development; Neurexin; Neuroligin; Synaptogenesis

Indexed keywords

4 AMINOBUTYRIC ACID;

ALTERNATIVE RNA SPLICING; AMINO ACID SEQUENCE; AUTISM; DEVELOPMENTAL DISORDER; FRAGILE X SYNDROME; GENE MUTATION; GENETIC POLYMORPHISM; HUMAN; NERVE CELL PLASTICITY; NONHUMAN; PHENOTYPE; PRADER WILLI SYNDROME; RETT SYNDROME; REVIEW; RISK FACTOR; SYNAPTIC TRANSMISSION;

EID: 84859993293     PISSN: None     EISSN: 16633563     Source Type: Journal    
DOI: 10.3389/fnsyn.2011.00001     Document Type: Review

References (96)

1. Abrahams, B. S., and Geschwind, D. H. (2008). Advances in autism genetics: on the threshold of a new neurobiology. Nat. Rev. Genet. 9, 341-355.
2. Arking, D. E., Cutler, D. J., Brune, C. W., Teslovich, T. M., West, K., Ikeda, M., Rea, A., Guy, M., Lin, S., Cook, E. H., and Chakravarti, A. (2008). A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am. J. Hum. Genet. 82, 160-164.
3. Ars, E., Serra, E., Garcia, J., Kruyer, H., Gaona, A., Lazaro, C., and Estivill, X. (2000). Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1. Hum. Mol. Genet. 9, 237-247.
4. Berkel, S., Marshall, C. R., Weiss, B., Howe, J., Roeth, R., Moog, U., Volker, E., Roberts, W., Szatmari, P., Pinto, D., Bonin, M., Riess, A., Engels, H., Sprengel, R., Scherer, S. W., and Rappold, G. A. (2010). Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation. Nat. Genet. 42, 489-491.
5. Betancur, C., Sakurai, T., and Buxbaum, J. D. (2009). The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders. Trends Neurosci. 32, 402-412.
6. Bhalla, K., Phillips, H. A., Crawford, J., McKenzie, O. L., Mulley, J. C., Eyre, H., Gardner, A. E., Kremmidiotis, G., and Callen, D. F. (2004). The de novo chromosome 16 translocations of two patients with abnormal phenotypes (mental retardation and epilepsy) disrupt the A2BP1 gene. J. Hum. Genet. 49, 308-311.
7. Bienvenu, T., and Chelly, J. (2006). Molecular genetics of Rett syndrome: when DNA methylation goes unrecognized. Nat. Rev. Genet. 7, 415-426.
8. Blasi, F., Bacchelli, E., Pesaresi, G., Carone, S., Bailey, A. J., and Maestrini, E. (2006). Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141B, 220-221.
9. Blundell, J., Tabuchi, K., Bolliger, M. F., Blaiss, C. A., Brose, N., Liu, X., Sudhof, T. C., and Powell, C. M. (2009). Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2. Genes Brain Behav. 8, 114-126.
10. Bonaglia, M. C., Giorda, R., Borgatti, R., Felisari, G., Gagliardi, C., Selicorni, A., and Zuffardi, O. (2001). Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated with the 22q13.3 deletion syndrome. Am. J. Hum. Genet. 69, 261-268.
11. Bonaglia, M. C., Giorda, R., Mani, E., Aceti, G., Anderlid, B. M., Baroncini, A., Pramparo, T., and Zuffardi, O. (2006). Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3 deletion syndrome. J. Med. Genet. 43, 822-828.
12. Boucard, A. A., Chubykin, A. A., Comoletti, D., Taylor, P., and Sudhof, T. C. (2005). A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to alpha- and beta-neurexins. Neuron 48, 229-236.
13. Cartegni, L., Chew, S. L., and Krainer, A. R. (2002). Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat. Rev. Genet. 3, 285-298.
14. Chih, B., Engelman, H., and Scheiffele, P. (2005). Control of excitatory and inhibitory synapse formation by neuroligins. Science 307, 1324-1328.
15. Chih, B., Gollan, L., and Scheiffele, P. (2006). Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex. Neuron 51, 171-178.
16. Chubykin, A. A., Atasoy, D., Etherton, M. R., Brose, N., Kavalali, E. T., Gibson, J. R., and Sudhof, T. C. (2007). Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2. Neuron 54, 919-931.
17. Comoletti, D., Flynn, R., Jennings, L. L., Chubykin, A., Matsumura, T., Hasegawa, H., Sudhof, T. C., and Taylor, P. (2003). Characterization of the interaction of a recombinant soluble neuroligin-1 with neurexin-1beta. J. Biol. Chem. 278, 50497-50505.
18. Cooper, T. A., Wan, L., and Dreyfuss, G. (2009). RNA and disease. Cell 136, 777-793.
19. Costa, R. M., Federov, N. B., Kogan, J. H., Murphy, G. G., Stern, J., Ohno, M., Kucherlapati, R., Jacks, T., and Silva, A. J. (2002). Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 415, 526-530.
20. Cusmano-Ozog, K., Manning, M. A., and Hoyme, H. E. (2007). 22q13.3 deletion syndrome: a recognizable malformation syndrome associated with marked speech and language delay. Am. J. Med. Genet. C Semin. Med. Genet. 145C, 393-398.
21. Dahlhaus, R., and El-Husseini, A. (2010). Altered neuroligin expression is involved in social deficits in a mouse model of the fragile X syndrome. Behav. Brain Res. 208, 96-105.
22. Darnell, J. C., Fraser, C. E., Mostovetsky, O., Stefani, G., Jones, T. A., Eddy, S. R., and Darnell, R. B. (2005). Kissing complex RNAs mediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes. Genes Dev. 19, 903-918.
23. Darnell, J. C., Jensen, K. B., Jin, P., Brown, V., Warren, S. T., and Darnell, R. B. (2001). Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 107, 489-499.
24. De Boulle, K., Verkerk, A. J., Reyniers, E., Vits, L., Hendrickx, J., Van Roy, B., Van den Bos, F., de Graaff, E., Oostra, B. A., and Willems, P. J. (1993). A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat. Genet. 3, 31-35.
25. Didiot, M. C., Tian, Z., Schaeffer, C., Subramanian, M., Mandel, J. L., and Moine, H. (2008). The G-quartet containing FMRP binding site in FMR1 mRNA is a potent exonic splicing enhancer. Nucleic Acids Res. 36, 4902-4912.
26. Dindot, S. V., Antalffy, B. A., Bhattacharjee, M. B., and Beaudet, A. L. (2008). The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology. Hum. Mol. Genet. 17, 111-118.
27. Durand, C. M., Betancur, C., Boeckers, T. M., Bockmann, J., Chaste, P., Fauchereau, F., Nygren, G., Rastam, M., Gillberg, I. C., Anckarsater, H., Sponheim, E., Goubran-Botros, H., Delorme, R., Chabane, N., Mouren-Simeoni, M. C., de Mas, P., Bieth, E., Roge, B., Heron, D., Burglen, L., Gillberg, C., Leboyer, M., and Bourgeron, T. (2007). Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat. Genet. 39, 25-27.
28. Eran, A., Graham, K. R., Vatalaro, K., McCarthy, J., Collins, C., Peters, H., Brewster, S. J., Hanson, E., Hundley, R., Rappaport, L., Holm, I. A., Kohane, I. S., and Kunkel, L. M. (2009). Comment on "Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients." J. Clin. Invest. 119, 679-680; author reply 680-671.
29. Fabrichny, I. P., Leone, P., Sulzenbacher, G., Comoletti, D., Miller, M. T., Taylor, P., Bourne, Y., and Marchot, P. (2007). Structural analysis of the synaptic protein neuroligin and its beta-neurexin complex: determinants for folding and cell adhesion. Neuron 56, 979-991.
30. Feng, J., Schroer, R., Yan, J., Song, W., Yang, C., Bockholt, A., Cook, E. H. Jr., Skinner, C., Schwartz, C. E., and Sommer, S. S. (2006). High frequency of neurexin 1beta signal peptide structural variants in patients with autism. Neurosci. Lett. 409, 10-13.
31. Fukumura, K., Kato, A., Jin, Y., Ideue, T., Hirose, T., Kataoka, N., Fujiwara, T., Sakamoto, H., and Inoue, K. (2007). Tissue-specific splicing regulator Fox-1 induces exon skipping by interfering E complex formation on the downstream intron of human F1gamma gene. Nucleic Acids Res. 35, 5303-5311.
32. Gauthier, J., Bonnel, A., St-Onge, J., Karemera, L., Laurent, S., Mottron, L., Fombonne, E., Joober, R., and Rouleau, G. A. (2005). NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population. Am. J. Med. Genet. B Neuropsychiatr. Genet. 132B, 74-75.
33. Gauthier, J., Spiegelman, D., Piton, A., Lafreniere, R. G., Laurent, S., St-Onge, J., Lapointe, L., Hamdan, F. F., Cossette, P., Mottron, L., Fombonne, E., Joober, R., Marineau, C., Drapeau, P., and Rouleau, G. A. (2009). Novel de novo SHANK3 mutation in autistic patients. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 421-424.
34. Gibson, J. R., Huber, K. M., and Sudhof, T. C. (2009). Neuroligin-2 deletion selectively decreases inhibitory synaptic transmission originating from fast-spiking but not from somatostatin-positive interneurons. J. Neurosci. 29, 13883-13897.
35. Heim, R. A., Silverman, L. M., Farber, R. A., Kam-Morgan, L. N., and Luce, M. C. (1994). Screening for truncated NF1 proteins. Nat. Genet. 8, 218-219.
36. Hines, R. M., Wu, L., Hines, D. J., Steenland, H., Mansour, S., Dahlhaus, R., Singaraja, R. R., Cao, X., Sammler, E., Hormuzdi, S. G., Zhuo, M., and El-Husseini, A. (2008). Synaptic imbalance, stereotypies, and impaired social interactions in mice with altered neuroligin 2 expression. J. Neurosci. 28, 6055-6067.
37. Horn, D. A., Suburo, A., Terenghi, G., Hudson, L. D., Polak, J. M., and Latchman, D. S. (1992). Expression of the tissue specific splicing protein SmN in neuronal cell lines and in regions of the brain with different splicing capacities. Brain Res. Mol. Brain Res. 16, 13-19.
38. Hsueh, Y. P. (2007). Neurofibromin signaling and synapses. J. Biomed. Sci. 14, 461-466.
39. Huang, Z. J., and Scheiffele, P. (2008). GABA and neuroligin signaling: linking synaptic activity and adhesion in inhibitory synapse development. Curr. Opin. Neurobiol. 18, 77-83.
40. Husi, H., Ward, M. A., Choudhary, J. S., Blackstock, W. P., and Grant, S. G. (2000). Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nat. Neurosci. 3, 661-669.
41. Jamain, S., Quach, H., Betancur, C., Rastam, M., Colineaux, C., Gillberg, I. C., Soderstrom, H., Giros, B., Leboyer, M., Gillberg, C., and Bourgeron, T. (2003). Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat. Genet. 34, 27-29.
42. Jin, Y., Suzuki, H., Maegawa, S., Endo, H., Sugano, S., Hashimoto, K., Yasuda, K., and Inoue, K. (2003). A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG. EMBO J. 22, 905-912.
43. Johnson, M. B., Kawasawa, Y. I., Mason, C. E., Krsnik, Z., Coppola, G., Bogdanovic, D., Geschwind, D. H., Mane, S. M., State, M. W., and Sestan, N. (2009). Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 62, 494-509.
44. Kang, Y., Zhang, X., Dobie, F., Wu, H., and Craig, A. M. (2008). Induction of GABAergic postsynaptic differentiation by alpha-neurexins. J. Biol. Chem. 283, 2323-2334.
45. Khandjian, E. W., Huot, M. E., Tremblay, S., Davidovic, L., Mazroui, R., and Bardoni, B. (2004). Biochemical evidence for the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparticles. Proc. Natl. Acad. Sci. U.S.A. 101, 13357-13362.
46. Kishore, S., Khanna, A., Zhang, Z., Hui, J., Balwierz, P. J., Stefan, M., Beach, C., Nicholls, R. D., Zavolan, M., and Stamm, S. (2010). The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing. Hum. Mol. Genet. 19, 1153-1164.
47. Kishore, S., and Stamm, S. (2006). The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C. Science 311, 230-232.
48. Ko, J., Fuccillo, M. V., Malenka, R. C., and Sudhof, T. C. (2009). LRRTM2 functions as a neurexin ligand in promoting excitatory synapse formation. Neuron 64, 791-798.
49. Laumonnier, F., Bonnet-Brilhault, F., Gomot, M., Blanc, R., David, A., Moizard, M. P., Raynaud, M., Ronce, N., Lemonnier, E., Calvas, P., Laudier, B., Chelly, J., Fryns, J. P., Ropers, H. H., Hamel, B. C., Andres, C., Barthelemy, C., Moraine, C., and Briault, S. (2004). X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am. J. Hum. Genet. 74, 552-557.
50. Lawson-Yuen, A., Saldivar, J. S., Sommer, S., and Picker, J. (2008). Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur. J. Hum. Genet. 16, 614-618.
51. Lee, J. A., Tang, Z. Z., and Black, D. L. (2009). An inducible change in Fox-1/A2BP1 splicing modulates the alternative splicing of downstream neuronal target exons. Genes Dev. 23, 2284-2293.
52. Li, C., Cheng, Y., Gutmann, D. A., and Mangoura, D. (2001). Differential localization of the neurofibromatosis 1 (NF1) gene product, neurofibromin, with the F-actin or microtubule cytoskeleton during differentiation of telencephalic neurons. Brain Res. Dev. Brain Res. 130, 231-248.
53. Li, Q., Lee, J. A., and Black, D. L. (2007). Neuronal regulation of alternative pre-mRNA splicing. Nat. Rev. Neurosci. 8, 819-831.
54. Licatalosi, D. D., Mele, A., Fak, J. J., Ule, J., Kayikci, M., Chi, S. W., Clark, T. A., Schweitzer, A. C., Blume, J. E., Wang, X., Darnell, J. C., and Darnell, R. B. (2008). HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature 456, 464-469.
55. Loat, C. S., Curran, S., Lewis, C. M., Duvall, J., Geschwind, D., Bolton, P., and Craig, I. W. (2008). Methyl-CpG-binding protein 2 polymorphisms and vulnerability to autism. Genes Brain Behav. 7, 754-760.
56. Lopez-Bigas, N., Audit, B., Ouzounis, C., Parra, G., and Guigo, R. (2005). Are splicing mutations the most frequent cause of hereditary disease? FEBS Lett. 579, 1900-1903.
57. Martin, C. L., Duvall, J. A., Ilkin, Y., Simon, J. S., Arreaza, M. G., Wilkes, K., Alvarez-Retuerto, A., Whichello, A., Powell, C. M., Rao, K., Cook, E., and Geschwind, D. H. (2007). Cytogenetic and molecular characterization of A2BP1/FOX1 as a candidate gene for autism. Am. J. Med. Genet. B Neuropsychiatr. Genet. 144B, 869-876.
58. Mayer, K., Ballhausen, W., Leistner, W., and Rott, H. (2000). Three novel types of splicing aberrations in the tuberous sclerosis TSC2 gene caused by mutations apart from splice consensus sequences. Biochim. Biophys. Acta 1502, 495-507.
59. Mayer, K., Ballhausen, W., and Rott, H. D. (1999). Mutation screening of the entire coding regions of the TSC1 and the TSC2 gene with the protein truncation test (PTT) identifies frequent splicing defects. Hum. Mutat. 14, 401-411.
60. Messiaen, L. M., Callens, T., Mortier, G., Beysen, D., Vandenbroucke, I., Van Roy, N., Speleman, F., and Paepe, A. D. (2000). Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. Hum. Mutat. 15, 541-555.
61. Minovitsky, S., Gee, S. L., Schokrpur, S., Dubchak, I., and Conboy, J. G. (2005). The splicing regulatory element, UGCAUG, is phylogenetically and spatially conserved in introns that flank tissue-specific alternative exons. Nucleic Acids Res. 33, 714-724.
62. Mount, R. H., Charman, T., Hastings, R. P., Reilly, S., and Cass, H. (2003). Features of autism in Rett syndrome and severe mental retardation. J. Autism Dev. Disord. 33, 435-442.
63. Narayanan, V. (2003). Tuberous sclerosis complex: genetics to pathogenesis. Pediatr. Neurol. 29, 404-409.
64. Pagenstecher, C., Wehner, M., Friedl, W., Rahner, N., Aretz, S., Friedrichs, N., Sengteller, M., Henn, W., Buettner, R., Propping, P., and Mangold, E. (2006). Aberrant splicing in MLH1 and MSH2 due to exonic and intronic variants. Hum. Genet. 119, 9-22.
65. Pampanos, A., Volaki, K., Kanavakis, E., Papandreou, O., Youroukos, S., Thomaidis, L., Karkelis, S., Tzetis, M., and Kitsiou-Tzeli, S. (2009). A substitution involving the NLGN4 gene associated with autistic behavior in the Greek population. Genet. Test Mol. Biomarkers 13, 611-615.
66. Pfannkuche, K., Hannes, T., Khalil, M., Noghabi, M. S., Morshedi, A., Hescheler, J., and Droge, P. (2010). Induced pluripotent stem cells: a new approach for physiological research. Cell. Physiol. Biochem. 26, 105-124.
67. Ponthier, J. L., Schluepen, C., Chen, W., Lersch, R. A., Gee, S. L., Hou, V. C., Lo, A. J., Short, S. A., Chasis, J. A., Winkelmann, J. C., and Conboy, J. G. (2006). Fox-2 splicing factor binds to a conserved intron motif to promote inclusion of protein 4.1R alternative exon 16. J. Biol. Chem. 281, 12468-12474.
68. Prabhakar, S., Noonan, J. P., Paabo, S., and Rubin, E. M. (2006). Accelerated evolution of conserved noncoding sequences in humans. Science 314, 786.
69. Roussignol, G., Ango, F., Romorini, S., Tu, J. C., Sala, C., Worley, P. F., Bockaert, J., and Fagni, L. (2005). Shank expression is sufficient to induce functional dendritic spine synapses in aspiny neurons. J. Neurosci. 25, 3560-3570.
70. Runte, M., Kroisel, P. M., Gillessen-Kaesbach, G., Varon, R., Horn, D., Cohen, M. Y., Wagstaff, J., Horsthemke, B., and Buiting, K. (2004). SNURF-SNRPN and UBE3A transcript levels in patients with Angelman syndrome. Hum. Genet. 114, 553-561.
71. Sadakata, T., Washida, M., Iwayama, Y., Shoji, S., Sato, Y., Ohkura, T., Katoh-Semba, R., Nakajima, M., Sekine, Y., Tanaka, M., Nakamura, K., Iwata, Y., Tsuchiya, K. J., Mori, N., Detera-Wadleigh, S. D., Ichikawa, H., Itohara, S., Yoshikawa, T., and Furuichi, T. (2007a). Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients. J. Clin. Invest. 117, 931-943.
72. Sadakata, T., Kakegawa, W., Mizoguchi, A., Washida, M., Katoh-Semba, R., Shutoh, F., Okamoto, T., Nakashima, H., Kimura, K., Tanaka, M., Sekine, Y., Itohara, S., Yuzaki, M., Nagao, S., and Furuichi, T. (2007b). Impaired cerebellar development and function in mice lacking CAPS2, a protein involved in neurotrophin release. J. Neurosci. 27, 2472-2482.
73. Schmauss, C., Brines, M. L., and Lerner, M. R. (1992). The gene encoding the small nuclear ribonucleoprotein-associated protein N is expressed at high levels in neurons. J. Biol. Chem. 267, 8521-8529.
74. Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., Leotta, A., Pai, D., Zhang, R., Lee, Y. H., Hicks, J., Spence, S. J., Lee, A. T., Puura, K., Lehtimaki, T., Ledbetter, D., Gregersen, P. K., Bregman, J., Sutcliffe, J. S., Jobanputra, V., Chung, W., Warburton, D., King, M. C., Skuse, D., Geschwind, D. H., Gilliam, T. C., Ye, K., and Wigler, M. (2007). Strong association of de novo copy number mutations with autism. Science 316, 445-449.
75. Shapiro, L., Love, J., and Colman, D. R. (2007). Adhesion molecules in the nervous system: structural insights into function and diversity. Annu. Rev. Neurosci. 30, 451-474.
76. Sittler, A., Devys, D., Weber, C., and Mandel, J. L. (1996). Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms. Hum. Mol. Genet. 5, 95-102.
77. Tabuchi, K., Blundell, J., Etherton, M. R., Hammer, R. E., Liu, X., Powell, C. M., and Sudhof, T. C. (2007). A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318, 71-76.
78. Talebizadeh, Z., Lam, D. Y., Theodoro, M. F., Bittel, D. C., Lushington, G. H., and Butler, M. G. (2006). Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism. J. Med. Genet. 43, e21.
79. Tavazoie, S. F., Alvarez, V. A., Ridenour, D. A., Kwiatkowski, D. J., and Sabatini, B. L. (2005). Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2. Nat. Neurosci. 8, 1727-1734.
80. Teraoka, S. N., Telatar, M., Becker-Catania, S., Liang, T., Onengüt, S., Tolun, A., Chessa, L., Sanal, O., Bernatowska, E., Gatti, R. A., and Concannon, P. (1999). Splicing defects in the ataxia-telangiectasia gene, ATM: underlying mutations and consequences. Am. J. Hum. Genet. 64, 1617-1631.
81. Underwood, J. G., Boutz, P. L., Dougherty, J. D., Stoilov, P., and Black, D. L. (2005). Homologues of the Caenorhabditis elegans Fox-1 protein are neuronal splicing regulators in mammals. Mol. Cell. Biol. 25, 10005-10016.
82. Varoqueaux, F., Aramuni, G., Rawson, R. L., Mohrmann, R., Missler, M., Gottmann, K., Zhang, W., Sudhof, T. C., and Brose, N. (2006). Neuroligins determine synapse maturation and function. Neuron 51, 741-754.
83. Veltman, M. W., Thompson, R. J., Roberts, S. E., Thomas, N. S., Whittington, J., and Bolton, P. F. (2004). Prader-Willi syndrome - a study comparing deletion and uniparental disomy cases with reference to autism spectrum disorders. Eur. Child. Adolesc. Psychiatry 13, 42-50.
84. Vincent, J. B., Kolozsvari, D., Roberts, W. S., Bolton, P. F., Gurling, H. M., and Scherer, S. W. (2004). Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands. Am. J. Med. Genet. B Neuropsychiatr. Genet. 129B, 82-84.
85. von der Brelie, C., Waltereit, R., Zhang, L., Beck, H., and Kirschstein, T. (2006). Impaired synaptic plasticity in a rat model of tuberous sclerosis. Eur. J. Neurosci. 23, 686-692.
86. Wang, G. S., and Cooper, T. A. (2007). Splicing in disease: disruption of the splicing code and the decoding machinery. Nat. Rev. Genet. 8, 749-761.
87. Xing, Y., and Lee, C. (2005). Evidence of functional selection pressure for alternative splicing events that accelerate evolution of protein subsequences. Proc. Natl. Acad. Sci. U.S.A. 102, 13526-13531.
88. Yan, J., Noltner, K., Feng, J., Li, W., Schroer, R., Skinner, C., Zeng, W., Schwartz, C. E., and Sommer, S. S. (2008). Neurexin 1alpha structural variants associated with autism. Neurosci. Lett. 438, 368-370.
89. Yan, J., Oliveira, G., Coutinho, A., Yang, C., Feng, J., Katz, C., Sram, J., Bockholt, A., Jones, I. R., Craddock, N., Cook, E. H., Jr., Vicente, A., and Sommer, S. S. (2005). Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Mol. Psychiatry 10, 329-332.
90. Ylisaukko-oja, T., Rehnstrom, K., Auranen, M., Vanhala, R., Alen, R., Kempas, E., Ellonen, P., Turunen, J. A., Makkonen, I., Riikonen, R., Nieminen-von Wendt, T., von Wendt, L., Peltonen, L., and Jarvela, I. (2005). Analysis of four neuroligin genes as candidates for autism. Eur. J. Hum. Genet. 13, 1285-1292.
91. Young, J. I., Hong, E. P., Castle, J. C., Crespo-Barreto, J., Bowman, A. B., Rose, M. F., Kang, D., Richman, R., Johnson, J. M., Berget, S., and Zoghbi, H. Y. (2005). Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. Proc. Natl. Acad. Sci. U.S.A. 102, 17551-17558.
92. Zafeiriou, D. I., Ververi, A., and Vargiami, E. (2007). Childhood autism and associated comorbidities. Brain Dev. 29, 257-272.
93. Zhang, C., Zhang, Z., Castle, J., Sun, S., Johnson, J., Krainer, A. R., and Zhang, M. Q. (2008). Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2. Genes Dev. 22, 2550-2563.
94. Zhang, Y., Bertolino, A., Fazio, L., Blasi, G., Rampino, A., Romano, R., Lee, M. L., Xiao, T., Papp, A., Wang, D., and Sadee, W. (2007). Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory. Proc. Natl. Acad. Sci. U.S.A. 104, 20552-20557.
95. Zhou, H. L., and Lou, H. (2008). Repression of prespliceosome complex formation at two distinct steps by Fox-1/Fox-2 proteins. Mol. Cell. Biol. 28, 5507-5516.
96. Zhou, Z., Licklider, L. J., Gygi, S. P., and Reed, R. (2002). Comprehensive proteomic analysis of the human spliceosome. Nature 419, 182-185.