Journal of Genetic Medicine

  • 제12권1호
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  • Pages.19-24
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  • 2015
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  • 1226-1769(pISSN)
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  • 2383-8442(eISSN)
대한의학유전학회 (Korean Society of Medical Genetics and Genomics)
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Recent advances in genetic studies of stuttering

  • Kang, Changsoo (Department of Biology and Research Institute of Basic Sciences, Sungshin Women's University)
  • 투고 : 2015.05.31
  • 심사 : 2015.06.04
  • 발행 : 2015.06.30
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초록

Speech and language are uniquely human-specific traits, which contributed to humans becoming the predominant species on earth. Disruptions in the human speech and language function may result in diverse disorders. These include stuttering, aphasia, articulation disorder, spasmodic dysphonia, verbal dyspraxia, dyslexia and specific language impairment. Among these disorders, stuttering is the most common speech disorder characterized by disruptions in the normal flow of speech. Twin, adoption, and family studies have suggested that genetic factors are involved in susceptibility to stuttering. For several decades, multiple genetic studies including linkage analysis were performed to connect causative gene to stuttering, and several genetic studies have revealed the association of specific gene mutation with stuttering. One notable genetic discovery came from the genetic studies in the consanguineous Pakistani families. These studies suggested that mutations in the lysosomal enzyme-targeting pathway genes (GNPTAB, GNPTG and NAPGA) are associated with non-syndromic persistent stuttering. Although these studies have revealed some clues in understanding the genetic causes of stuttering, only a small fraction of patients are affected by these genes. In this study, we summarize recent advances and future challenges in an effort to understand genetic causes underlying stuttering.

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참고문헌

  1. Kang C, Drayna D. Genetics of speech and language disorders. Annu Rev Genomics Hum Genet 2011;12:145-64. https://doi.org/10.1146/annurev-genom-090810-183119
  2. Holy TE, Guo Z. Ultrasonic songs of male mice. PLoS Biol 2005;3:e386. https://doi.org/10.1371/journal.pbio.0030386
  3. White SA, Fisher SE, Geschwind DH, Scharff C, Holy TE. Singing mice, songbirds, and more: models for FOXP2 function and dysfunction in human speech and language. J Neurosci 2006;26:10376-9. https://doi.org/10.1523/JNEUROSCI.3379-06.2006
  4. Bloodstein O. A handbook on stuttering. 6th ed. Clifton Park, NY: Thomson Delmar Learning, 2008.
  5. Cole M, Wright D, Banker BQ. Familial aphasia: the Pick-Alzheimer spectrum. Trans Am Neurol Assoc 1979;104:175-9.
  6. Lera G, Bhatia K, Marsden CD. Dystonia as the major manifestation of Leigh's syndrome. Mov Disord 1994;9:642-9. https://doi.org/10.1002/mds.870090610
  7. Drayna D, Kilshaw J, Kelly J. The sex ratio in familial persistent stuttering. Am J Hum Genet 1999;65:1473-5. https://doi.org/10.1086/302625
  8. Dworzynski K, Remington A, Rijsdijk F, Howell P, Plomin R. Genetic etiology in cases of recovered and persistent stuttering in an unselected, longitudinal sample of young twins. Am J Speech Lang Pathol 2007;16:169-78. https://doi.org/10.1044/1058-0360(2007/021)
  9. Howie PM. Concordance for stuttering in monozygotic and dizygotic twin pairs. J Speech Hear Res 1981;24:317-21. https://doi.org/10.1044/jshr.2403.317
  10. Raza MH, Amjad R, Riazuddin S, Drayna D. Studies in a consanguineous family reveal a novel locus for stuttering on chromosome 16q. Hum Genet 2012;131:311-3. https://doi.org/10.1007/s00439-011-1134-2
  11. Raza MH, Gertz EM, Mundorff J, Lukong J, Kuster J, Schaffer AA, et al. Linkage analysis of a large African family segregating stuttering suggests polygenic inheritance. Hum Genet 2013;132:385-96. https://doi.org/10.1007/s00439-012-1252-5
  12. Raza MH, Riazuddin S, Drayna D. Identification of an autosomal recessive stuttering locus on chromosome 3q13.2-3q13.33. Hum Genet 2010;128:461-3. https://doi.org/10.1007/s00439-010-0871-y
  13. Riaz N, Steinberg S, Ahmad J, Pluzhnikov A, Riazuddin S, Cox NJ, et al. Genomewide significant linkage to stuttering on chromosome 12. Am J Hum Genet 2005;76:647-51. https://doi.org/10.1086/429226
  14. Kang C, Riazuddin S, Mundorff J, Krasnewich D, Friedman P, Mullikin JC, et al. Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering. N Engl J Med 2010;362:677-85. https://doi.org/10.1056/NEJMoa0902630
  15. Suresh R, Ambrose N, Roe C, Pluzhnikov A, Wittke-Thompson JK, Ng MC, et al. New complexities in the genetics of stuttering: significant sex-specific linkage signals. Am J Hum Genet 2006;78:554-63. https://doi.org/10.1086/501370
  16. Felsenfeld S, Plomin R. Epidemiological and offspring analyses of developmental speech disorders using data from the Colorado Adoption Project. J Speech Lang Hear Res 1997;40:778-91. https://doi.org/10.1044/jslhr.4004.778
  17. Cox NJ, Kramer PL, Kidd KK. Segregation analyses of stuttering. Genet Epidemiol 1984;1:245-53. https://doi.org/10.1002/gepi.1370010304
  18. Shugart YY, Mundorff J, Kilshaw J, Doheny K, Doan B, Wanyee J, et al. Results of a genome-wide linkage scan for stuttering. Am J Med Genet A 2004;124A:133-5. https://doi.org/10.1002/ajmg.a.20347
  19. Wittke-Thompson JK, Ambrose N, Yairi E, Roe C, Cook EH, Ober C, et al. Genetic studies of stuttering in a founder population. J Fluency Disord 2007;32:33-50. https://doi.org/10.1016/j.jfludis.2006.12.002
  20. Fedyna A, Drayna D, Kang C. Characterization of a mutation commonly associated with persistent stuttering: evidence for a founder mutation. J Hum Genet 2011;56:80-2. https://doi.org/10.1038/jhg.2010.125
  21. Bao M, Booth JL, Elmendorf BJ, Canfield WM. Bovine UDP-N-acetylglucosamine:lysosomal-enzyme N-acetylglucosamine-1-phosphotransferase. I. Purification and subunit structure. J Biol Chem 1996;271:31437-45. https://doi.org/10.1074/jbc.271.49.31437
  22. Kornfeld S. Trafficking of lysosomal enzymes in normal and disease states. J Clin Invest 1986;77:1-6. https://doi.org/10.1172/JCI112262
  23. Otomo T, Muramatsu T, Yorifuji T, Okuyama T, Nakabayashi H, Fukao T, et al. Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype-phenotype correlation. J Hum Genet 2009;54:145-51. https://doi.org/10.1038/jhg.2009.3
  24. Paik KH, Song SM, Ki CS, Yu HW, Kim JS, Min KH, et al. Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA. Hum Mutat 2005;2:308-14.
  25. Tiede S, Storch S, Lübke T, Henrissat B, Bargal R, Raas-Rothschild A, et al. Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase. Nat Med 2005;11:1109-12. https://doi.org/10.1038/nm1305
  26. Smuts I, Potgieter D, van der Westhuizen FH. Combined tarsal and carpal tunnel syndrome in mucolipidosis type III. A case study and review. Ann N Y Acad Sci 2009;1151:77-84. https://doi.org/10.1111/j.1749-6632.2008.03451.x
  27. Do H, Lee WS, Ghosh P, Hollowell T, Canfield W, Kornfeld S. Human mannose 6-phosphate-uncovering enzyme is synthesized as a proenzyme that is activated by the endoprotease furin. J Biol Chem 2002;277:29737-44. https://doi.org/10.1074/jbc.M202369200
  28. Lee WS, Kang C, Drayna D, Kornfeld S. Analysis of mannose 6-phosphate uncovering enzyme mutations associated with persistent stuttering. J Biol Chem 2011;286:39786-93. https://doi.org/10.1074/jbc.M111.295899