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OTİZM GENETİĞİ

Yıl 2005, Cilt: 36 Sayı: 1, 35 - 41, 17.07.2014

Adnan Yüksel

Öz

Otizm merkezi sinir sisteminin gelişimsel bir bozukluğudur. Günümüze kadar etiyolojisi tam olarak saptanamamıştır. Otizmin bazı tipleri tek başına veya genetik sendromun bir parçası olarak kalıtsal olmakla birlikte bir kısmı çevresel faktörler ile ortaya çıkmaktadır.  Günümüze kadar yapılan aile ve ikiz çalışmaları hastalığın etiyolojisinde genetik faktörlerin önemli bir rol oynadığını göstermiştir. Hastalığın hem lokus hem de allelik heterojenite gösterdiği, kalıtım tipinin ise eşik değerli multifaktöryel kalıtım modeli ile uygunluk gösterdiği saptanmıştır.  Günümüzde otizm genetiğiyle ilgili, kromozom anomalilerinin incelenmesi, ilişki  çalışmaları ve genetik bağlantı analiz çalışmaları hızlı bir şekilde devam etmektedir. Otistik olgularda hem yapısal hem de sayısal çok sayıda kromozom anomalisi bildirilmiştir. İlişki ve genetik bağlantı çalışmalarında hasta seçme kriterlerinin farklı olması, farklı genetik markırların kullanılması, genetik harita ve  istatistik analizlerinin değişkenliğinden dolayı farklı sonuçlar bulunmuştur. Bununla birlikte 7 kromozom bölgesinde (2, 3, 7, 11, 15, 17, X kromozomları) maksimum Lod skor anlamlı bulunmuştur. Günümüzde otistik hastalarda, kromozom 3’te GAT1 ve OXTR, kromozom 7’de FOXP2, WNT2, RELN, HOXA1 ve HOXB1, kromozom 11’de HRAS, kromozom 15’de GABRB3, GABRA5, GABRG3, UBE3A ve ATP10C, kromozom 17’de 5-HTT, kromozom X’de MeCP2, NLGN3 ve NLGN4 genlerinde çeşitli değişiklikler saptanmış olup bu genler  üzerinde yoğun çalışmalar sürmektedir.

Anahtar Kelimeler

Otizm genetik

Kaynakça

  • 1. Davidovicz HM. Autistic Spectrum Disorder. In: Frank Y. Pediatric Behavioral Neurology CRC Press, Boca Raton, 1996; 73-87.
  • 2. Volmar FR, Pauls D. Autism. Lancet 2003; 362: 1133-41. 3. Wing L. The autitic spectrum. Lancet 1997; 350: 1761- 66.
  • 4. Folstein SE, Rosen-Sheidley B. Genetics of autism: Complex aetiology for a heterogenous disorder. Nat Rev Genet 2001; 2: 943–55.
  • 5. Lamb JA, Moore J, Bailey A, et al. Monaco AP. Autism: Recent molecular genetic advances. Hum Mol Genet 2000; 9: 861-8.
  • 6. Newschaffer CJ, Fallin D, Lee NL. Heritable and Nonheritable risk factors for autism spectrum disorders. Epi Rev 2002; 24: 137-53.
  • 7. Kanner L. Autistic disturbances of affective contact. Nerv Child 1943; 2: 217–50.
  • 8. Kanner L, Eisenberg L. Child psychiatry; mental deficiency. Am J Psychiatry. 1956; 112: 531-4.
  • 9. Gillberg C, Coleman M. Autism and medical disorders: A review of the literature. Dev Med Child Neurol 1996; 38: 191–202.
  • 10. Brown WT, Jenkins EC, Cohen IL, et al. Fragile X and autism: A multicenter survey. Am J Med Genet 1986; 23: 341–52.
  • 11. Deykin EY, MacMahon B. Pregnancy, delivery, and neonatal complications among autistic children. Am J Dis Child 1980; 134: 860–4.
  • 12. Piven J, Simon J, Chase GA, et al. The etiology of autism: Pre-, peri-, and neonatal factors. J Am Acad Child Adolesc Psychiatry 1993; 32: 1256–63.
  • 13. Bolton PF, Murphy M, Macdonald H, et al. Obstetric complications in autism. Consequences or causes of the condition? J Am Acad Child Adolesc Psychiatry 1997; 36: 272–81.
  • 14. Mason-Brothers A, Ritvo ER, Pingree C, et al. The UCLA-University of Utah epidemiologic survey of autism: Prenatal, perinatal, and postnatal factors. Pediatrics 1990; 86: 514–19.
  • 15. Burd L, Severud R, Kerbeshian J, et al. Prenatal and perinatal risk factors for autism. J Perinat Med 1999; 27: 441–50.
  • 16. Deykin EY, MacMahon B. Viral exposure and autism. Am J Epidemiol 1979; 109: 628–38.
  • 17. Halsey NA, Hyman SL. Measles-mumps-rubella vaccine and autistic spectrum disorder: Report from the New Challenges in Childhood Immunizations Conference convened in Oak Brook, Illinois, June 12–13, 2000. Pediatrics 2001; 107: E84.
  • 18. Madsen K, Hvid A, Vestergaard M, et al. A populationbased study of measles, mumps, and rubella vaccination and autism. N Engl J Med 2002; 347: 1477–82.
  • 19. Bernard S, Enayati A, Redwood L, et al. Autism: A novel form of mercury poisoning. Med Hypotheses 2001; 56: 462–71.
  • 20. Stromland K, Nordin V, Miller M, et al. Autism in thalidomide embryopathy: A population study. Dev Med Child Neurol 1994; 36: 351–6.
  • 21. Zimmerman AW. The immune system in autism. J Dev Learn Disord 1999; 3: 3–15.
  • 22. Nelson KB, Grether JK, Croen LA, et al. Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. Ann Neurol 2001; 49: 597- 606.
  • 23. Folstein S, Rutter M. Infantile autism: A genetic study of 21 twin pairs. J Child Psychol Psychiatry 1977; 18: 297- 321.
  • 24. Ritvo ER, Freeman BJ, Mason-Brothers A, et al. Concordance for the syndrome of autism in 40 pairs of afflicted twins. Am J Psychiatry 1985; 142: 74–7.
  • 25. Steffenburg S, Gillberg C, Hellgren L, et al. A twin study of autism in Denmark, Finland, Iceland, Norway, and Sweden. J Child Psychol Psychiatry 1989; 30: 405–16.
  • 26. Ritvo ER, Jorde LB, Mason-Brothers A, et al. The UCLA-University of Utah epidemiologic survey of autism: Recurrence risk estimates and genetic counseling. Am J Psychiatry 1989; 146: 1032–6.
  • 27. Jorde LB, Hasstedt SJ, Ritvo ER, Mason-Brothers A, Freeman BJ, Pingree C, McMahon WM, Petersen B, Jenson WR, Mo A. Complex segregation analysis of autism. Am J Hum Genet. 1991; 49: 932-8.
  • 28. Szatmari P, Jones MB, Zwaigenbaum L, et al. Genetics of autism: Overview and new directions. J Autism Dev Disord 1998; 28: 351–68.
  • 29. Piven J. The broad autism phenotype: A complementary strategy for molecular genetic studies of autism. Am J Med Genet 2001; 105: 34–5.
  • 30. Gillberg C. Chromosomal disorders and autism. J Autism Dev Disord 1998; 28: 415–25.
  • 31. Wassink TH, Piven J, Patil SR. Chromosomal abnormalities in a clinic sample of individuals with autistic disorder. Psychiatr Genet 2001; 11: 57–63.
  • 32. Ashley-Koch A, Wolpert CM, Menold MM, et al. Genetic studies of autistic disorder and chromosome 7. Genomics 1999; 61: 227–36.
  • 33. Bass MP, Menold MM, Wolpert CM, et al. Genetic studies in autistic disorder and chromosome 15. Neurogenetics 2000; 2: 219–26
  • 34. Cook EH Jr, Lindgren V, Leventhal BL, et al. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet 1997; 60: 928–34.
  • 35. Schroer RJ, Phelan MC, Michaelis RC, et al. Autism and maternally derived aberration of chromosome 15q. Am J Med Genet 1998; 76: 327–33.
  • 36. Further characterization of the autism susceptibility locus AUTS1 on chromosome 7q. Hum Mol Genet 2001; 10: 973–82.
  • 37. A full genome screen for autism with evidence for linkage to a region on chromosome 7q. Hum Mol Genet 1998; 7: 571–8.
  • 38. A genomewide screen for autism: Strong evidence for linkage to chromosomes 2q, 7q, and 16p. International Molecular Genetic Study of Autism Consortium. Am J Hum Genet 2001; 69: 570–81.
  • 39. Li J, Tabor HK, Nguyen L, et al. Lack of association between HoxA1 and HoxB1 gene variants and autism in 110 multiplex families. Am J Med Genet 2002; 114: 24– 30.
  • 40. Persico AM, D’Agruma L, Maiorano N, et al. Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. Mol Psychiatry 2001; 6: 150–9.
  • 41. Martin ER, Menold MM, Wolpert CM, et al. Analysis of linkage disequilibrium in gamma-aminobutyric acid receptor subunit genes in autistic disorder. Am J Med Genet 2000; 96: 43–8.
  • 42. Maestrini E, Lai C, Marlow A, et al. Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the IMGSA families. The International Molecular Genetic Study of Autism Consortium. Am J Med Genet 1999; 88: 492–6.
  • 43. Yirmiya N, Pilowsky T, Nemanov L, et al. Evidence for an association with the serotonin transporter promoter region polymorphism and autism. Am J Med Genet 2001; 105: 381–6.
  • 44. Persico AM, Militerni R, Bravaccio C, et al. Lack of association between serotonin transporter gene promoter variants and autistic disorder in two ethnically distinct samples. Am J Med Genet 2000; 96: 123–7.
  • 45. Beyer KS, Blasi F, Bacchelli, Klauch SM, Maestrini R, Poustka A. Mutation analysis of the coding sequence of the MECP2 gene in infantil autism. Hum Genet 2002; 111: 305-9
  • 46. Auranen M, Nieminen T, Majuri S, et al. Analysis of autism susceptibility gene loci on chromosomes 1p, 4p, 6q, 7q, 13q, 15q, 16p, 17q, 19q, and 22q in Finnish multiplex families. Mol Psychiatry 2000; 5: 320–2.
  • 47. Yonan AL, Alarcon M, Cheng R, Magnusson PK, Spence SJ, Palmer AA, Grunn A, Juo SH, Terwilliger JD, Liu J, Cantor RM, Geschwind DH, Gilliam TC. A genomewide screen of 345 families for autism-susceptibility loci.Am J Hum Genet 2003; 73: 886-97
  • 48. Philippe A, Martinez M, Guilloud-Bataille M, et al. Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study. Hum Mol Genet 1999; 8: 805–12.

Yıl 2005, Cilt: 36 Sayı: 1, 35 - 41, 17.07.2014

Adnan Yüksel

Öz

Kaynakça

  • 1. Davidovicz HM. Autistic Spectrum Disorder. In: Frank Y. Pediatric Behavioral Neurology CRC Press, Boca Raton, 1996; 73-87.
  • 2. Volmar FR, Pauls D. Autism. Lancet 2003; 362: 1133-41. 3. Wing L. The autitic spectrum. Lancet 1997; 350: 1761- 66.
  • 4. Folstein SE, Rosen-Sheidley B. Genetics of autism: Complex aetiology for a heterogenous disorder. Nat Rev Genet 2001; 2: 943–55.
  • 5. Lamb JA, Moore J, Bailey A, et al. Monaco AP. Autism: Recent molecular genetic advances. Hum Mol Genet 2000; 9: 861-8.
  • 6. Newschaffer CJ, Fallin D, Lee NL. Heritable and Nonheritable risk factors for autism spectrum disorders. Epi Rev 2002; 24: 137-53.
  • 7. Kanner L. Autistic disturbances of affective contact. Nerv Child 1943; 2: 217–50.
  • 8. Kanner L, Eisenberg L. Child psychiatry; mental deficiency. Am J Psychiatry. 1956; 112: 531-4.
  • 9. Gillberg C, Coleman M. Autism and medical disorders: A review of the literature. Dev Med Child Neurol 1996; 38: 191–202.
  • 10. Brown WT, Jenkins EC, Cohen IL, et al. Fragile X and autism: A multicenter survey. Am J Med Genet 1986; 23: 341–52.
  • 11. Deykin EY, MacMahon B. Pregnancy, delivery, and neonatal complications among autistic children. Am J Dis Child 1980; 134: 860–4.
  • 12. Piven J, Simon J, Chase GA, et al. The etiology of autism: Pre-, peri-, and neonatal factors. J Am Acad Child Adolesc Psychiatry 1993; 32: 1256–63.
  • 13. Bolton PF, Murphy M, Macdonald H, et al. Obstetric complications in autism. Consequences or causes of the condition? J Am Acad Child Adolesc Psychiatry 1997; 36: 272–81.
  • 14. Mason-Brothers A, Ritvo ER, Pingree C, et al. The UCLA-University of Utah epidemiologic survey of autism: Prenatal, perinatal, and postnatal factors. Pediatrics 1990; 86: 514–19.
  • 15. Burd L, Severud R, Kerbeshian J, et al. Prenatal and perinatal risk factors for autism. J Perinat Med 1999; 27: 441–50.
  • 16. Deykin EY, MacMahon B. Viral exposure and autism. Am J Epidemiol 1979; 109: 628–38.
  • 17. Halsey NA, Hyman SL. Measles-mumps-rubella vaccine and autistic spectrum disorder: Report from the New Challenges in Childhood Immunizations Conference convened in Oak Brook, Illinois, June 12–13, 2000. Pediatrics 2001; 107: E84.
  • 18. Madsen K, Hvid A, Vestergaard M, et al. A populationbased study of measles, mumps, and rubella vaccination and autism. N Engl J Med 2002; 347: 1477–82.
  • 19. Bernard S, Enayati A, Redwood L, et al. Autism: A novel form of mercury poisoning. Med Hypotheses 2001; 56: 462–71.
  • 20. Stromland K, Nordin V, Miller M, et al. Autism in thalidomide embryopathy: A population study. Dev Med Child Neurol 1994; 36: 351–6.
  • 21. Zimmerman AW. The immune system in autism. J Dev Learn Disord 1999; 3: 3–15.
  • 22. Nelson KB, Grether JK, Croen LA, et al. Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. Ann Neurol 2001; 49: 597- 606.
  • 23. Folstein S, Rutter M. Infantile autism: A genetic study of 21 twin pairs. J Child Psychol Psychiatry 1977; 18: 297- 321.
  • 24. Ritvo ER, Freeman BJ, Mason-Brothers A, et al. Concordance for the syndrome of autism in 40 pairs of afflicted twins. Am J Psychiatry 1985; 142: 74–7.
  • 25. Steffenburg S, Gillberg C, Hellgren L, et al. A twin study of autism in Denmark, Finland, Iceland, Norway, and Sweden. J Child Psychol Psychiatry 1989; 30: 405–16.
  • 26. Ritvo ER, Jorde LB, Mason-Brothers A, et al. The UCLA-University of Utah epidemiologic survey of autism: Recurrence risk estimates and genetic counseling. Am J Psychiatry 1989; 146: 1032–6.
  • 27. Jorde LB, Hasstedt SJ, Ritvo ER, Mason-Brothers A, Freeman BJ, Pingree C, McMahon WM, Petersen B, Jenson WR, Mo A. Complex segregation analysis of autism. Am J Hum Genet. 1991; 49: 932-8.
  • 28. Szatmari P, Jones MB, Zwaigenbaum L, et al. Genetics of autism: Overview and new directions. J Autism Dev Disord 1998; 28: 351–68.
  • 29. Piven J. The broad autism phenotype: A complementary strategy for molecular genetic studies of autism. Am J Med Genet 2001; 105: 34–5.
  • 30. Gillberg C. Chromosomal disorders and autism. J Autism Dev Disord 1998; 28: 415–25.
  • 31. Wassink TH, Piven J, Patil SR. Chromosomal abnormalities in a clinic sample of individuals with autistic disorder. Psychiatr Genet 2001; 11: 57–63.
  • 32. Ashley-Koch A, Wolpert CM, Menold MM, et al. Genetic studies of autistic disorder and chromosome 7. Genomics 1999; 61: 227–36.
  • 33. Bass MP, Menold MM, Wolpert CM, et al. Genetic studies in autistic disorder and chromosome 15. Neurogenetics 2000; 2: 219–26
  • 34. Cook EH Jr, Lindgren V, Leventhal BL, et al. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet 1997; 60: 928–34.
  • 35. Schroer RJ, Phelan MC, Michaelis RC, et al. Autism and maternally derived aberration of chromosome 15q. Am J Med Genet 1998; 76: 327–33.
  • 36. Further characterization of the autism susceptibility locus AUTS1 on chromosome 7q. Hum Mol Genet 2001; 10: 973–82.
  • 37. A full genome screen for autism with evidence for linkage to a region on chromosome 7q. Hum Mol Genet 1998; 7: 571–8.
  • 38. A genomewide screen for autism: Strong evidence for linkage to chromosomes 2q, 7q, and 16p. International Molecular Genetic Study of Autism Consortium. Am J Hum Genet 2001; 69: 570–81.
  • 39. Li J, Tabor HK, Nguyen L, et al. Lack of association between HoxA1 and HoxB1 gene variants and autism in 110 multiplex families. Am J Med Genet 2002; 114: 24– 30.
  • 40. Persico AM, D’Agruma L, Maiorano N, et al. Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. Mol Psychiatry 2001; 6: 150–9.
  • 41. Martin ER, Menold MM, Wolpert CM, et al. Analysis of linkage disequilibrium in gamma-aminobutyric acid receptor subunit genes in autistic disorder. Am J Med Genet 2000; 96: 43–8.
  • 42. Maestrini E, Lai C, Marlow A, et al. Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the IMGSA families. The International Molecular Genetic Study of Autism Consortium. Am J Med Genet 1999; 88: 492–6.
  • 43. Yirmiya N, Pilowsky T, Nemanov L, et al. Evidence for an association with the serotonin transporter promoter region polymorphism and autism. Am J Med Genet 2001; 105: 381–6.
  • 44. Persico AM, Militerni R, Bravaccio C, et al. Lack of association between serotonin transporter gene promoter variants and autistic disorder in two ethnically distinct samples. Am J Med Genet 2000; 96: 123–7.
  • 45. Beyer KS, Blasi F, Bacchelli, Klauch SM, Maestrini R, Poustka A. Mutation analysis of the coding sequence of the MECP2 gene in infantil autism. Hum Genet 2002; 111: 305-9
  • 46. Auranen M, Nieminen T, Majuri S, et al. Analysis of autism susceptibility gene loci on chromosomes 1p, 4p, 6q, 7q, 13q, 15q, 16p, 17q, 19q, and 22q in Finnish multiplex families. Mol Psychiatry 2000; 5: 320–2.
  • 47. Yonan AL, Alarcon M, Cheng R, Magnusson PK, Spence SJ, Palmer AA, Grunn A, Juo SH, Terwilliger JD, Liu J, Cantor RM, Geschwind DH, Gilliam TC. A genomewide screen of 345 families for autism-susceptibility loci.Am J Hum Genet 2003; 73: 886-97
  • 48. Philippe A, Martinez M, Guilloud-Bataille M, et al. Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study. Hum Mol Genet 1999; 8: 805–12.
Toplam 47 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Derlemeler
Yazarlar

Adnan Yüksel Bu kişi benim

Yayımlanma Tarihi 17 Temmuz 2014
Yayımlandığı Sayı Yıl 2005 Cilt: 36 Sayı: 1

Kaynak Göster

APA Yüksel, A. (2014). OTİZM GENETİĞİ. Cerrahpaşa Tıp Dergisi, 36(1), 35-41.
AMA Yüksel A. OTİZM GENETİĞİ. Cerrahpaşa Tıp Dergisi. Temmuz 2014;36(1):35-41.
Chicago Yüksel, Adnan. “OTİZM GENETİĞİ”. Cerrahpaşa Tıp Dergisi 36, sy. 1 (Temmuz 2014): 35-41.
EndNote Yüksel A (01 Temmuz 2014) OTİZM GENETİĞİ. Cerrahpaşa Tıp Dergisi 36 1 35–41.
IEEE A. Yüksel, “OTİZM GENETİĞİ”, Cerrahpaşa Tıp Dergisi, c. 36, sy. 1, ss. 35–41, 2014.
ISNAD Yüksel, Adnan. “OTİZM GENETİĞİ”. Cerrahpaşa Tıp Dergisi 36/1 (Temmuz 2014), 35-41.
JAMA Yüksel A. OTİZM GENETİĞİ. Cerrahpaşa Tıp Dergisi. 2014;36:35–41.
MLA Yüksel, Adnan. “OTİZM GENETİĞİ”. Cerrahpaşa Tıp Dergisi, c. 36, sy. 1, 2014, ss. 35-41.
Vancouver Yüksel A. OTİZM GENETİĞİ. Cerrahpaşa Tıp Dergisi. 2014;36(1):35-41.