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OTİZMİN GENETİK TEMELLLERİ

Year 2013, Volume: 22 Issue: 1, 86 - 92, 01.03.2013

Abstract

Otistik bozukluk toplumsal ve iletişimsel sorunları yaşamları boyunca süren çocukları ve erişkinleri içine alan, özellikle erkeklerde (4:1) daha sık görülen yaygın gelişimsel bir bozukluktur. Yineleyici-sınırlayıcı hareketler dışında iletişim ve bilişsel gelişimde gecikme ya da sapma ile karakterizedir. Otizm etiyolojisinin bilinmemesine rağmen yapılan çalışmalar hastalığın oluşmasında genetik faktörlerin büyük rol oynadığını göstermiştir. Otistik çocukların kardeşlerinde otizm görülme riskinin sağlıklı bireylerin kardeşlerinden 30-150 kat yüksek olduğu tespit edilmiştir. Otizm üzerindeki son dönem araştırmalar genetik, beyin işlevleri, nörokimyasal ve immünolojik etkenler üzerine yoğunlaşmıştır. Bağlantı ve ilişki çalışmaları ile belirli kromozom bölgelerinde (2, 3, 7, 11, 15, 17, X kromozomları) anlamlı sonuçlar bulunmuştur. Otizm için bilinmeyenlerin ışığında ayırıcı tanıda yol gösterebilecek, tedaviye yanıtı öngörebilecek veya ölçebilecek biyolojik belirteçler saptanmasının önemi büyüktür. Bu derleme otizmin genetik kökeni hakkında kısa bir özet verilmesi ve otizme sebep olabileceği düşünülen genetik faktörlerin gözden geçirilmesi amacıyla yazılmıştır

References

  • Wermter AK, Kamp-Becker I, Hesse P, et al. Evidence For The Involvement of Genetic Variation In The Oxytocin Receptor Gene (OXTR) In The Etiology Of Autistic Disorders On High-Functioning Level. Am J Med Genet Neuropsychiatric Genet Part B 2010; 153: 629 -639.
  • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 1994, 4th ed. Washington DC: American Psy- chiatric Press.
  • Keskin S, Alkış H. Otizm ve Pediatrist. Yeni Symposium 2001; 39: 35-38.
  • Pehlivantürk B. Otistik Bozukluğu Olan Ço- cuklarda Bağlanma. Türk Psikiyatri Dergisi 2004; 15: 56-63.
  • Kanner L. Autistic disturbances of affective contact. Nervous Child 1943; 2:217–250.
  • Baykara B. Otistik Çocukların Anne ve Baba- larında Geniş Otizm Fenotipinin Nörobilişsel Görünümünün Araştırılması. Uzmanlık Tezi, Dokuz Eylül Üniversitesi Tıp Fakültesi, İzmir 2003.
  • Ma DQ, Rabionet R, Konidari I, et al. Associa- tion and Gene–Gene Interaction of SLC6A4 and ITGB3 in Autism. Am J Med Genet Neuro- psychiatric Genet Part B 2009; 153: 477–483.
  • O’Roak BJ, State MW. Autism Genetics: Strategies, Challenges and Oppurtunities. Au- tism Research 2008; 1: 4-17.
  • Öztürk A. Otizm Genetiği. Cerrahpaşa Tıp Dergisi 2005; 36: 35-41.
  • James JS, Melnyk S, Jernigan S, et al. Abnor- mal Transmethylation/transsulfuration Me- tabolism and DNA Hypomethylation Among Parents of Children with Autism. J Autism Dev Disord 2008; 38:1966–1975.
  • Levy SE, David S Mandell, Robert T Schultz. Autism. Lancet 2009; 374: 1627–1638.
  • Dawson G, Devlin B, Estes A, et al. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nature Genet- ics 2007; 39: 319-328.
  • Tuna-Ulay H, Ertuğrul A. Otizmde Beyin Gö- rüntüleme Bulguları: Bir Gözden Geçirme. Türk Psikiyatri Dergisi 2009; 20: 164-174.
  • Trevathan E. Seizures and Epilepsy Among Children With Language Regression and Autistic Spectrum Disorders. J Child Neurol 2004; 19: 49-S57
  • Valicenti-McDermott M, McVicar K, Rapin I, et al. Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoim- mune disease. J Dev Behav Pediatr 2006; 27:128-136.
  • Trottier G, Srivastava L, Walker CD. Etiology of infantile autism: a review of recent ad- vances in genetic and neurobiological re- search. J Psychiatry Neurosci 1999; 24:103- 15.
  • Lauritsen M, Ewald H. The genetics of autism. Acta Psychiatr Scand 2001; 103:411-27.
  • Jyonouchi H, Geng L, Streck DL, et al. Immunological transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): case study. J Neuroinflammation 2012; 9:4.
  • Ziats MN, Rennert OM. Expression Profiling of Autism Candidate Genes during Human Brain Development Implicates Central Immune Signaling Pathways. PLoS One 2011; 6:24691.
  • Malik M, Sheikh AM, Wen G, et al. Expression of inflammatory cytokines, Bcl2 and cathepsin D are altered in lymphoblasts of autistic subjects. Immunobiology 2011; 216:80–85.
  • Philippi A, Tores F, Carayol J, et al. Associa- tion of autism with polymorphisms in the paired-like homeodomain transcription factor 1 (PITX1) on chromosome 5q31: a candidate gene analysis. BMC Medical Genetics 2007; 8: 1-8.
  • Miles JH. Autism spectrum disorders A genet- ics review. Genet Med 2011: 13:278–294.
  • Yang SY, Cho SC, Yoo HJ, et al. Association Study Between Single Nucleotide Polymor- phisms In Promoter Region of AVPR1A and Korean Autism Spectrum Disorders. Neurosci- ence Letters 2010; 479:197-200.
  • Weiss LA, Arking DE. A genome-wide linkage and association scan reveals novel loci for autism. Nature 2009; 461: 802-808.
  • Moss J, Howlin P. Autism spectrum disorders in genetic syndromes: implications for diagno- sis, intervention and understanding the wider autism spectrum disorder population. J Intel- lect Disabil Res 2009; 53:852-73.
  • Autism Genome Project Consortium, Szatmari P, Paterson AD, et al. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nature Genet 2007; 39: 319– 328.
  • El-Fishawy P, State MW. The Genetics of Au- tism: Key Issues, Recent Findings, and Clinical Implications. Psychiatr Clin N Am 2010; 33:83 –105.
  • Campbell DB, Sutcliffe JS, Ebert PJ, et al. A genetic variant that disrupts MET transcrip- tion is associated with autism. Proc Natl Acad Sci USA 2006; 103:16834-16839.
  • Russo AJ, Krigsman A, Jepson B, et al. De- creased Serum Hepatocyte Growth Factor (HGF) in Autistic Children with Severe Gas- trointestinal Disease. Biomarker Insights 2009; 2:181–190.
  • Tan GCY, Doke TF, Ashburner J, et al. Normal variation in fronto-occipital circuitry and cere- bellar structure with an autism-associated polymorphism of CNTNAP2. Neuroimage 2010; 53:1030–1042.
  • Alarcón M, Abrahams B, Stone J, et al. Link- age, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am J Hum Genet 2008; 82:150-9.
  • Arking DE, Cutler DJ, Brune CW, et al. A common genetic variant in the neurexin super- family member CNTNAP2 increases familial risk of autism. Am J Hum Genet. 2008; 82:160 -4.
  • Bakkaloglu B, O'Roak BJ, Louvi A, et al. Mo- lecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am J Hum Genet 2008; 82:165-173.
  • Rossi E, Verri AP, Patricelli MG, et al. A 12 Mb deletion at 7q33–q35 associated with au- tism spectrum disorders and primary amenor- rhea. Eur J Med Genet 2008; 51:631-638.
  • Rubenstein JLR. Three Hypotheses For Devel- opmental Defects That May Underlie Some Forms of Autism Spectrum Disorders. Current Opinion In Neurology 2010; 23: 118-123.
  • Bamshad MJ, Ng SB, Bigham AW, et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nature Reviews 2011; 12(11): 745-55.
  • Puffenberger EG, Jinks RN, Wang H, et al. A Homozygous Missense Mutation in HERC2 Associated with Global Developmental Delay and Autism Spectrum Disorder. Human Muta- tion 2012; 33: 1639-46.
  • Steinberg KM, Ramachandran D, Patel VC, et al. Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder. Molecu- lar Autism 2012; 28:8.
  • Nava C, Lamari F, D He´ron D, et al. Analy- sis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE. Transl Psychiatry 2012; 23: 179.
  • Yu TW, Chahrour MH, Coulter ME, Jiraler- spong S, Okamura-Ikeda K, Ataman B, Schmitz -Abe K, et al. Using Whole-Exome Sequencing to Identify Inherited Causes of Autism. Neuron 2013; 77:259-273.
  • Taneli Y. Yaygın Gelişimsel Bozuklukta Apoli poprotein E Gen Polimorfizminin Moleküler Genetik Yöntemle Araştırılması. Doktora Tezi, Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü Farmokoloji ve Klinik Farmakoloji Anabilim Dalı, Bursa 2006.

The Genetic Basis of Autism

Year 2013, Volume: 22 Issue: 1, 86 - 92, 01.03.2013

Abstract

Autistic spectrum disorder is a neuropsychiatric disorder which begins in the early years of life with delays and deviance in social, communicative and cognitive development and with restricted repertoire of activities and interests. Autism affects males four times more than females. Although the etiology of autism is unknown, evidence indicates that genetic factors play a major role in this disorder. The sibling recurrence risk of autism for additional children in families with an autistic child is 30-150 times greater than the population prevalence. Recent studies have focused on genetics, brain function, neurochemical and immunological factors. Significant results were found in several different chromosome regions (2, 3, 7, 11, 15, 17, X) with linkage and association studies. It is of great importance to detect biological markers for the differential diagnosis of autism. This review was written to give short information about the genetic basis of autism and for the revision of genetic factors thought to have a role in the etiology of autism

References

  • Wermter AK, Kamp-Becker I, Hesse P, et al. Evidence For The Involvement of Genetic Variation In The Oxytocin Receptor Gene (OXTR) In The Etiology Of Autistic Disorders On High-Functioning Level. Am J Med Genet Neuropsychiatric Genet Part B 2010; 153: 629 -639.
  • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 1994, 4th ed. Washington DC: American Psy- chiatric Press.
  • Keskin S, Alkış H. Otizm ve Pediatrist. Yeni Symposium 2001; 39: 35-38.
  • Pehlivantürk B. Otistik Bozukluğu Olan Ço- cuklarda Bağlanma. Türk Psikiyatri Dergisi 2004; 15: 56-63.
  • Kanner L. Autistic disturbances of affective contact. Nervous Child 1943; 2:217–250.
  • Baykara B. Otistik Çocukların Anne ve Baba- larında Geniş Otizm Fenotipinin Nörobilişsel Görünümünün Araştırılması. Uzmanlık Tezi, Dokuz Eylül Üniversitesi Tıp Fakültesi, İzmir 2003.
  • Ma DQ, Rabionet R, Konidari I, et al. Associa- tion and Gene–Gene Interaction of SLC6A4 and ITGB3 in Autism. Am J Med Genet Neuro- psychiatric Genet Part B 2009; 153: 477–483.
  • O’Roak BJ, State MW. Autism Genetics: Strategies, Challenges and Oppurtunities. Au- tism Research 2008; 1: 4-17.
  • Öztürk A. Otizm Genetiği. Cerrahpaşa Tıp Dergisi 2005; 36: 35-41.
  • James JS, Melnyk S, Jernigan S, et al. Abnor- mal Transmethylation/transsulfuration Me- tabolism and DNA Hypomethylation Among Parents of Children with Autism. J Autism Dev Disord 2008; 38:1966–1975.
  • Levy SE, David S Mandell, Robert T Schultz. Autism. Lancet 2009; 374: 1627–1638.
  • Dawson G, Devlin B, Estes A, et al. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nature Genet- ics 2007; 39: 319-328.
  • Tuna-Ulay H, Ertuğrul A. Otizmde Beyin Gö- rüntüleme Bulguları: Bir Gözden Geçirme. Türk Psikiyatri Dergisi 2009; 20: 164-174.
  • Trevathan E. Seizures and Epilepsy Among Children With Language Regression and Autistic Spectrum Disorders. J Child Neurol 2004; 19: 49-S57
  • Valicenti-McDermott M, McVicar K, Rapin I, et al. Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoim- mune disease. J Dev Behav Pediatr 2006; 27:128-136.
  • Trottier G, Srivastava L, Walker CD. Etiology of infantile autism: a review of recent ad- vances in genetic and neurobiological re- search. J Psychiatry Neurosci 1999; 24:103- 15.
  • Lauritsen M, Ewald H. The genetics of autism. Acta Psychiatr Scand 2001; 103:411-27.
  • Jyonouchi H, Geng L, Streck DL, et al. Immunological transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): case study. J Neuroinflammation 2012; 9:4.
  • Ziats MN, Rennert OM. Expression Profiling of Autism Candidate Genes during Human Brain Development Implicates Central Immune Signaling Pathways. PLoS One 2011; 6:24691.
  • Malik M, Sheikh AM, Wen G, et al. Expression of inflammatory cytokines, Bcl2 and cathepsin D are altered in lymphoblasts of autistic subjects. Immunobiology 2011; 216:80–85.
  • Philippi A, Tores F, Carayol J, et al. Associa- tion of autism with polymorphisms in the paired-like homeodomain transcription factor 1 (PITX1) on chromosome 5q31: a candidate gene analysis. BMC Medical Genetics 2007; 8: 1-8.
  • Miles JH. Autism spectrum disorders A genet- ics review. Genet Med 2011: 13:278–294.
  • Yang SY, Cho SC, Yoo HJ, et al. Association Study Between Single Nucleotide Polymor- phisms In Promoter Region of AVPR1A and Korean Autism Spectrum Disorders. Neurosci- ence Letters 2010; 479:197-200.
  • Weiss LA, Arking DE. A genome-wide linkage and association scan reveals novel loci for autism. Nature 2009; 461: 802-808.
  • Moss J, Howlin P. Autism spectrum disorders in genetic syndromes: implications for diagno- sis, intervention and understanding the wider autism spectrum disorder population. J Intel- lect Disabil Res 2009; 53:852-73.
  • Autism Genome Project Consortium, Szatmari P, Paterson AD, et al. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nature Genet 2007; 39: 319– 328.
  • El-Fishawy P, State MW. The Genetics of Au- tism: Key Issues, Recent Findings, and Clinical Implications. Psychiatr Clin N Am 2010; 33:83 –105.
  • Campbell DB, Sutcliffe JS, Ebert PJ, et al. A genetic variant that disrupts MET transcrip- tion is associated with autism. Proc Natl Acad Sci USA 2006; 103:16834-16839.
  • Russo AJ, Krigsman A, Jepson B, et al. De- creased Serum Hepatocyte Growth Factor (HGF) in Autistic Children with Severe Gas- trointestinal Disease. Biomarker Insights 2009; 2:181–190.
  • Tan GCY, Doke TF, Ashburner J, et al. Normal variation in fronto-occipital circuitry and cere- bellar structure with an autism-associated polymorphism of CNTNAP2. Neuroimage 2010; 53:1030–1042.
  • Alarcón M, Abrahams B, Stone J, et al. Link- age, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am J Hum Genet 2008; 82:150-9.
  • Arking DE, Cutler DJ, Brune CW, et al. A common genetic variant in the neurexin super- family member CNTNAP2 increases familial risk of autism. Am J Hum Genet. 2008; 82:160 -4.
  • Bakkaloglu B, O'Roak BJ, Louvi A, et al. Mo- lecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am J Hum Genet 2008; 82:165-173.
  • Rossi E, Verri AP, Patricelli MG, et al. A 12 Mb deletion at 7q33–q35 associated with au- tism spectrum disorders and primary amenor- rhea. Eur J Med Genet 2008; 51:631-638.
  • Rubenstein JLR. Three Hypotheses For Devel- opmental Defects That May Underlie Some Forms of Autism Spectrum Disorders. Current Opinion In Neurology 2010; 23: 118-123.
  • Bamshad MJ, Ng SB, Bigham AW, et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nature Reviews 2011; 12(11): 745-55.
  • Puffenberger EG, Jinks RN, Wang H, et al. A Homozygous Missense Mutation in HERC2 Associated with Global Developmental Delay and Autism Spectrum Disorder. Human Muta- tion 2012; 33: 1639-46.
  • Steinberg KM, Ramachandran D, Patel VC, et al. Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder. Molecu- lar Autism 2012; 28:8.
  • Nava C, Lamari F, D He´ron D, et al. Analy- sis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE. Transl Psychiatry 2012; 23: 179.
  • Yu TW, Chahrour MH, Coulter ME, Jiraler- spong S, Okamura-Ikeda K, Ataman B, Schmitz -Abe K, et al. Using Whole-Exome Sequencing to Identify Inherited Causes of Autism. Neuron 2013; 77:259-273.
  • Taneli Y. Yaygın Gelişimsel Bozuklukta Apoli poprotein E Gen Polimorfizminin Moleküler Genetik Yöntemle Araştırılması. Doktora Tezi, Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü Farmokoloji ve Klinik Farmakoloji Anabilim Dalı, Bursa 2006.
There are 41 citations in total.

Details

Other ID JA23VM34ZJ
Journal Section Collection
Authors

Elif Funda Şener This is me

Yusuf Özkul This is me

Publication Date March 1, 2013
Submission Date March 1, 2013
Published in Issue Year 2013 Volume: 22 Issue: 1

Cite

APA Şener, E. F., & Özkul, Y. (2013). OTİZMİN GENETİK TEMELLLERİ. Sağlık Bilimleri Dergisi, 22(1), 86-92.
AMA Şener EF, Özkul Y. OTİZMİN GENETİK TEMELLLERİ. JHS. March 2013;22(1):86-92.
Chicago Şener, Elif Funda, and Yusuf Özkul. “OTİZMİN GENETİK TEMELLLERİ”. Sağlık Bilimleri Dergisi 22, no. 1 (March 2013): 86-92.
EndNote Şener EF, Özkul Y (March 1, 2013) OTİZMİN GENETİK TEMELLLERİ. Sağlık Bilimleri Dergisi 22 1 86–92.
IEEE E. F. Şener and Y. Özkul, “OTİZMİN GENETİK TEMELLLERİ”, JHS, vol. 22, no. 1, pp. 86–92, 2013.
ISNAD Şener, Elif Funda - Özkul, Yusuf. “OTİZMİN GENETİK TEMELLLERİ”. Sağlık Bilimleri Dergisi 22/1 (March 2013), 86-92.
JAMA Şener EF, Özkul Y. OTİZMİN GENETİK TEMELLLERİ. JHS. 2013;22:86–92.
MLA Şener, Elif Funda and Yusuf Özkul. “OTİZMİN GENETİK TEMELLLERİ”. Sağlık Bilimleri Dergisi, vol. 22, no. 1, 2013, pp. 86-92.
Vancouver Şener EF, Özkul Y. OTİZMİN GENETİK TEMELLLERİ. JHS. 2013;22(1):86-92.