Abstract
The objective of this study was to detect the effect of Shank3 gene expression levels and their related to speech ability, education and social communication in children with Autism Spectrum Disorders. Forty ASD patients who were admitted to the (Rahman Specialist Centre for the care and service autistic children/ Baghdad/Iraq) and ten children apparently healthy group. Patients and healthy control group aged from (3-10) years. According the sex the results showed a significant increase in male (77.5%) compare to female (22.5%). Patients with ASD recorded a weak ability to speech in high significance increase (72.5%) compared to another group. While the ability to education and ability to social communication were moderate in high significant increase (65.5%) in patient with ASD. The quantitative Real-Time PCR Results showed a significant decreased (0.374 ±0.18) in ASD patients when compared to the healthy control group (1.00 ±0.00). The down-regulation of Shank3 appear a positive correlation to Ability to Speech, Ability to Education and Ability to social communication.
References
1. Tomchek SD, Dunn W. Sensory processing in children with and without autism: a comparative study using the short sensory profile. Am J Occup Ther. 2007;61(2): 190–200.
2. Moore DJ. Acute pain experience in individuals with autism spectrum disorders: a review. Autism. 2015;19:387-399.
3. Phelan K, McDermid HE (2012) The 22q13.3 Deletion Syndrome (PhelanMcDermid Syndrome). Mol Syndromol 2: 186–201.
4. Mitchell, K.J. (2010) The genetics of neurodevelopmental disease. Curr. Opin. Neurobiol ., 21, 1–7
5. Geschwind DH (2009) Advances in autism. Annu Rev Med 60: 367–380.
6. Huguet G, Ey E, Bourgeron T (2013) The Genetic Landscapes of Autism Spectrum Disorders. Annu Rev Genomics Hum Genet 14: 191–213.
7. Sudhof TC (2008) Neuroligins and neurexins link synaptic function to cognitive
disease. Nature 455: 903–911
8. Toro R, Konyukh M, Delorme R, Leblond C, Chaste P, et al. (2010) Key role for gene dosage and synaptic homeostasis in autism spectrum disorders. Trends Genet 26: 363–372
9. Leblond.C.L, Nava.C, Polge.A, Gauthier.J, Guillaume Huguet,G. et al., : Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments. PLOS genetics.2014;10(9): 1-15
10. Livak, K.J. and Schmittgen, T.D. ( 2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔ CT Method. Methods. 25, 402–408
11. SAS. (2004). SAS / STAT Users Guide for Personal Computers. Release 7.0. SAS Institute Inc., Cary, NC., USA. (SAS = Statistical Analysis System).
12. Yang M, Bozdagi O, Scattoni ML, Wöhr M, Roullet FI, Katz AM, et al., (2012) Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J Neurosci 32:6525–6541
13. Kouser M, Speed HE, Dewey CM, Reimers JM, Widman AJ, Gupta N, Liu S, et al., (2013) Loss of predominant Shank3 isoforms results in hippocampus-dependent impairments in behavior and synaptic transmission. J Neurosci 33:18448–18468.
14. South M, Newton T, Chamberlain PD (2012).Delayed reversal learning and association with repetitive behavior in autism spectrum disorders. Autism Res 5:398–406.
15. Leblond CS, Nava C, Polge A, Gauthier J, Huguet G, Lumbroso S, Giuliano F, et al., (2014) Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments. PLoS Genet 10:e1004580
16. Jaramillo TC, Speed HE, Xuan Z, Reimers JM, Escamilla CO, Weaver TP,et al., (2017) Novel Shank3 mutant exhibits behaviors with face validity for autism and altered striatal and hippocampal function. Autism Res 10:42–65.
17. Jiang YH, Ehlers MD (2013). Modeling autism by SHANK gene mutations in mice. Neuron 78:8–27.
18. Tachibana Y, Miyazaki C, Ota E, Mori R, Hwang Y, Kobayashi E, Terasaka A, Tang J, Kamio Y (2017) A systematic review and meta-analysis of comprehensive interventions for pre-school children with autism spectrum disorder. PLoS One 12: e0186502
19. Mitz AR, Philyaw TJ, Boccuto L, Shcheglovitov A, Sarasua SM, Kaufmann WE, Thurm A (2018) Identification of 22q13 genes most likely to contribute to Phelan McDermid syndrome. Eur J Hum Genet 26:293–302
20. Bonaglia, M. C., Giorda, R., Mani, E., Aceti, G., Anderlid, B. M., Baroncini, A.,et al., (2006). Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3 deletion syndrome. J.Med.Genet. 43, 822-828.
21. Kadhim,B. Al-Kazaz, Abdul-Kareem and and Al. Deresawi,M.S. (2015). Molecular Genetics Study on Autostatic patients in iraq. Iraq Journal of Science.56(1).
22. Gauthier, J., Bonnel, A., St Onge, J., Karemera, L., Laurent, S., Mottron, L., et al., (2005). NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population. Am.J.Med.Genet.B Neuropsychiatr.Genet. 132, 74-75.
23. Reboucas E.; Costa J.; Passos M.; Passos J.; Hurk R. and Silva J. (2013). Real Time PCR and Importance of Housekeeping’s Genes for Normalization and Quantification of mRNA Expression in Different Tissues. Brazil Arch Biol Technol. 56: 143-154
24. Barber D. (2005). GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiological Genomics; vol. 21 (3): 389-395.
25. Robert B.; Harmer W.; Coleman A. and Clark B. (2005). GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiol Genom. 21: 389–395.
26. American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Association.
27. Pérez E, Acero-Ferrero M and Herrero ML.(2019). Improvement of Planning Skills in Children With Autism Spectrum Disorder After an Educational Intervention: A Study From a Mixed Methods Approach. Front Psychol. 17;10:2824.
28. Lee, S., and Odom, S.L. (1996). The Relationship between Stereotypic Behavior and Peer Social Interaction for Children with Severe Disabilities. Research and Practice for Persons with Severe Disabilities, 21, 88 - 95.
29. De Rubeis S., Siper P. M., Durkin A., et al.(2018). Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations. Molecular Autism. 9(1):1–20.
30. Durand C. M., Betancur C., Boeckers T. M., et al.(2007). Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nature Genetics. (1):25–27.
31. Mei Y., Monteiro P., Zhou Y., et al.(2016). Adult restoration of Shank3 expression rescues selective autistic-like phenotypes. Nature. 530(7591):481–484.
32. Ponson L., Gomot M., Blanc R., et al. (2018).22q13 deletion syndrome: communication disorder or autism? Evidence from a specific clinical and neurophysiological phenotype. Translational Psychiatry. 8(1)
33. Gauthier J., Champagne N., Lafrenière R. G., et al.(2010). De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. Proceedings of the National Academy of Sciences. 107(17):7863–7868.
34. Moessner R., Marshall C. R., Sutcliffe J. S., et al(2007). Contribution of SHANK3 mutations to autism spectrum disorder. The American Journal of Human Genetics.;81(6):1289–1297.
35. Soorya L., Kolevzon A., Zweifach J., et al.(2013). Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency. Molecular Autism. 4(1):18–17.
36. Boccuto L., Lauri M., Sarasua S. M., et al.(2013). Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders. European Journal of Human Genetics. 21(3):310–316.
37. Peça J., Feliciano C., Ting J. T., et al.(2011). Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature. 2011;472(7344):437–442.
38. Rendall A. R., Perrino P. A., Buscarello A. N., Fitch R. H. (2019). Shank3B mutant mice display pitch discrimination enhancements and learning deficits. International Journal of Developmental Neuroscience. 72(1):13–21.
39. Remington A., Fairnie J. A sound advantage: increased auditory capacity in autism. Cognition. 2017;166:459–465..
40. de Sena Cortabitarte A., Degenhardt F., Strohmaier J., et al.(2017).Investigation of SHANK3 in schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 174(4):390–398.
41. Waga, Chikakoa; Okamoto, Nobuhikoc; Ondo, Yumikoa; Fukumura-Kato, Reikoa; et al.,( 2011). Novel variants of the SHANK3 gene in Japanese autistic patients with severe delayed speech development. Psychiatric Genetics 21(4):p 208-211,
42. Reboucas E.; Costa J.; Passos M.; Passos J.; Hurk R. and Silva J. (2013). Real Time PCR and Importance of Housekeepings Genes for Normalization and Quantification of mRNA Expression in Different Tissues. Brazil Arch Biol Technol. 56: 143-154.
43. Barber D. (2005). GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiological Genomics; vol. 21 (3): 389-395.
44. Robert B.; Harmer W.; Coleman A. and Clark B. (2005). GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiol Genom. 21: 389–395.