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Autism and cytogenetic abnormalities: Solving autism one chromosome at a time

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Abstract

Autism is a neurodevelopmental disorder characterized by impairments in social interactions, communication, and behavior. Multiple lines of evidence support the notion that most cases of autism likely have an underlying genetic cause or predisposition. Like mental retardation, autism is likely to be caused by many different genetic mechanisms and genes rather than a single, or few, major genes or environmental effects. In this review, we will focus on the cytogenetic contribution to uncovering regions of the genome involved in autism. Some common cytogenetic imbalances already known to cause autism will be highlighted. Routine genetic testing in clinical (CLIA-certified) diagnostic laboratories can identify the specific etiology and recurrence risk in 10% to 15% of autism cases and is clinically indicated for any child with autism. Powerful new methods for identifying novel regions of the genome causing or contributing to autism also will be discussed and will start to explain the etiology for some percentage of the remaining 85% to 90% of autism cases.

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References and Recommended Reading

  1. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, edn 4, text revision edn. Washington, DC: American Psychiatric Association; 2000.

    Google Scholar 

  2. Scahill L: Diagnosis and evaluation of pervasive developmental disorders. J Clin Psychiatry 2005, 66(Suppl 10):19–25.

    PubMed  Google Scholar 

  3. Yeargin-Allsopp M, Rice C, Karapurkar T, et al.: Prevalence of autism in a US metropolitan area. JAMA 2003, 289:49–55.

    Article  PubMed  Google Scholar 

  4. Muhle R, Trentacoste SV, Rapin I: The genetics of autism. Pediatrics 2004, 113:e472–e486.

    Article  PubMed  Google Scholar 

  5. Veenstra-VanderWeele J, Cook EH, Jr: Molecular genetics of autism spectrum disorder. Mol Psychiatry 2004, 9:819–832.

    Article  PubMed  CAS  Google Scholar 

  6. Castermans D, Wilquet V, Steyaert J, et al.: Chromosomal anomalies in individuals with autism: a strategy towards the identification of genes involved in autism. Autism 2004, 8:141–161.

    Article  PubMed  Google Scholar 

  7. Cook EH, Jr: Genetics of autism. Child Adolesc Psychiatr Clin N Am 2001, 10:333–350.

    PubMed  Google Scholar 

  8. Fombonne E, Du Mazaubrun C, Cans C, Grandjean H: Autism and associated medical disorders in a French epidemiological survey. J Am Acad Child Adolesc Psychiatry 1997, 36:1561–1569.

    Article  PubMed  CAS  Google Scholar 

  9. Lewis KE, Lubetsky MJ, Wenger SL, Steele MW: Chromosomal abnormalities in a psychiatric population. Am J Med Genet 1995, 60:53–54.

    Article  PubMed  CAS  Google Scholar 

  10. Wassink TH, Piven J, Patil SR: Chromosomal abnormalities in a clinic sample of individuals with autistic disorder. Psychiatr Genet 2001, 11:57–63.

    Article  PubMed  CAS  Google Scholar 

  11. Veenstra-Vanderweele J, Christian SL, Cook EH, Jr: Autism as a paradigmatic complex genetic disorder. Annu Rev Genomics Hum Genet 2004, 5:379–405.

    Article  PubMed  CAS  Google Scholar 

  12. Vorstman JA, Staal WG, van Daalen E, et al.: Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism. Mol Psychiatry 2006, 11:1, 18–28.

    Article  PubMed  CAS  Google Scholar 

  13. Manning MA, Cassidy SB, Clericuzio C, et al.: Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum. Pediatrics 2004, 114:451–457.

    Article  PubMed  Google Scholar 

  14. Wolff DJ, Clifton K, Karr C, Charles J: Pilot assessment of the subtelomeric regions of children with autism: detection of a 2q deletion. Genet Med 2002, 4:10–14.

    PubMed  Google Scholar 

  15. de Vries BB, Pfundt R, Leisink M, et al.: Diagnostic genome profiling in mental retardation. Am J Hum Genet 2005, 77:606–616.

    Article  PubMed  Google Scholar 

  16. Rauch A, Ruschendorf F, Huang J, et al.: Molecular karyotyping using an SNP array for genomewide genotyping. J Med Genet 2004, 41:916–922.

    Article  PubMed  CAS  Google Scholar 

  17. Pinkel D, Segraves R, Sudar D, et al.: High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 1998, 20:207–211.

    Article  PubMed  CAS  Google Scholar 

  18. Lubs HA: A marker X chromosome. Am J Hum Genet 1969, 21:231–244.

    PubMed  CAS  Google Scholar 

  19. Verkerk AJ, Pieretti M, Sutcliffe JS, et al.: Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991, 65:905–914.

    Article  PubMed  CAS  Google Scholar 

  20. Visootsak J, Warren ST, Anido A, Graham JM, Jr: Fragile X syndrome: an update and review for the primary pediatrician. Clin Pediatr (Phila) 2005, 44:371–381.

    Article  Google Scholar 

  21. 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, 60:928–934.

    PubMed  CAS  Google Scholar 

  22. Schroer RJ, Phelan MC, Michaelis RC, et al.: Autism and maternally derived aberrations of chromosome 15q. Am J Med Genet 1998, 76:327–336.

    Article  PubMed  CAS  Google Scholar 

  23. Wolpert C, Pericak-Vance MA, Abramson RK, et al.: Autistic symptoms among children and young adults with isodicentric chromosome 15. Am J Med Genet 2000, 96:128–129.

    Article  PubMed  CAS  Google Scholar 

  24. Moeschler JB, Mohandas TK, Hawk AB, Noll WW: Estimate of prevalence of proximal 15q duplication syndrome. Am J Med Genet 2002, 111:440–442.

    Article  PubMed  Google Scholar 

  25. Battaglia A: The inv dup(15) or idic(15) syndrome: a clinically recognisable neurogenetic disorder. Brain Dev 2005, 27:365–369.

    Article  PubMed  Google Scholar 

  26. Dennis NR, Veltman MW, Thompson R, et al.: Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11–q13. - 441.

  27. Ungaro P, Christian SL, Fantes JA, et al.: Molecular characterisation of four cases of intrachromosomal triplication of chromosome 15q11-q14. J Med Genet 2001, 38:26–34.

    Article  PubMed  CAS  Google Scholar 

  28. Casas KA, Mononen TK, Mikail CN, et al.: Chromosome 2q terminal deletion: report of 6 new patients and review of phenotype-breakpoint correlations in 66 individuals. Am J Med Genet A 2004, 130:331–339.

    Article  Google Scholar 

  29. Ghaziuddin M, Burmeister M: Deletion of chromosome 2q37 and autism: a distinct subtype? J Autism Dev Disord 1999, 29:259–263.

    Article  PubMed  CAS  Google Scholar 

  30. Lukusa T, Vermeesch JR, Holvoet M, et al.: Deletion 2q37.3 and autism: molecular cytogenetic mapping of the candidate region for autistic disorder. Genet Couns 2004, 15:293–301.

    PubMed  CAS  Google Scholar 

  31. Smith M, Escamilla JR, Filipek P, et al.: Molecular genetic delineation of 2q37.3 deletion in autism and osteodystrophy: report of a case and of new markers for deletion screening by PCR. Cytogenet Cell Genet 2001, 94:15–22.

    Article  PubMed  CAS  Google Scholar 

  32. Wassink TH, Piven J, Vieland VJ, et al.: Evaluation of the chromosome 2q37.3 gene CENTG2 as an autism susceptibility gene. Am J Med Genet B Neuropsychiatr Genet 2005, 136:36–44.

    Google Scholar 

  33. Aldred MA, Sanford RO, Thomas NS, et al.: Molecular analysis of 20 patients with 2q37.3 monosomy: definition of minimum deletion intervals for key phenotypes. J Med Genet 2004, 41:433–439.

    Article  PubMed  CAS  Google Scholar 

  34. Tezenas Du Montcel S, Mendizabai H, Ayme S, et al.: Prevalence of 22q11 microdeletion. J Med Genet 1996, 33:719.

    Article  PubMed  CAS  Google Scholar 

  35. Niklasson L, Rasmussen P, Oskarsdottir S, Gillberg C: Neuropsychiatric disorders in the 22q11 deletion syndrome. Genet Med 2001, 3:79–84.

    Article  PubMed  CAS  Google Scholar 

  36. Fine SE, Weissman A, Gerdes M, et al.: Autism spectrum disorders and symptoms in children with molecularly confirmed 22q11.2 deletion syndrome. J Autism Dev Disord 2005, 35:461–470.

    Article  PubMed  Google Scholar 

  37. Vorstman JA, Morcus ME, Duijff SN, et al.: The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry 2006, 45:1104–1113.

    Article  PubMed  Google Scholar 

  38. Flint J, Wilkie AO, Buckle VJ, et al.: The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat Genet 1995, 9:132–140.

    Article  PubMed  CAS  Google Scholar 

  39. Phelan MC, Rogers RC, Saul RA, et al.: 22q13 deletion syndrome. Am J Med Genet 2001, 101:91–99.

    Article  PubMed  CAS  Google Scholar 

  40. Wilson HL, Wong AC, Shaw SR, et al.: Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. J Med Genet 2003, 40:575–584.

    Article  PubMed  CAS  Google Scholar 

  41. Precht KS, Lese CM, Spiro RP, et al.: Two 22q telomere deletions serendipitously detected by FISH. J Med Genet 1998, 35:939–942.

    Article  PubMed  CAS  Google Scholar 

  42. Prasad C, Prasad AN, Chodirker BN, et al.: Genetic evaluation of pervasive developmental disorders: The terminal 22q13 deletion syndrome may represent a recognizable phenotype. Clin Genet 2000, 57:103–109.

    Article  PubMed  CAS  Google Scholar 

  43. Goizet C, Excoffier E, Taine L, et al.: Case with autistic syndrome and chromosome 22q13.3 deletion detected by FISH. Am J Med Genet 2000, 96:839–844.

    Article  PubMed  CAS  Google Scholar 

  44. Jeffries AR, Curran S, Elmslie F, et al.: Molecular and phenotypic characterization of ring chromosome 22. Am J Med Genet A 2005, 137:139–147.

    PubMed  Google Scholar 

  45. Friedman JM, Baross A, Delaney AD, et al.: Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation. Am J Hum Genet 2006, 79:500–513.

    Article  PubMed  CAS  Google Scholar 

  46. Shaw-Smith C, Redon R, Rickman L, et al.: Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features. J Med Genet 2004, 41:241–248.

    Article  PubMed  CAS  Google Scholar 

  47. Jacquemont ML, Sanlaville D, Redon R, et al.: Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders. J Med Genet 2006, 43:843–849.

    Article  PubMed  CAS  Google Scholar 

  48. Tuzun E, Sharp AJ, Bailey JA, et al.: Fine-scale structural variation of the human genome. Nat Genet 2005, 37:727–732.

    Article  PubMed  CAS  Google Scholar 

  49. Iafrate AJ, Feuk L, Rivera MN, et al.: Detection of largescale variation in the human genome. Nat Genet 2004, 36:949–951.

    Article  PubMed  CAS  Google Scholar 

  50. Sebat J, Lakshmi B, Troge J, et al.: Large-scale copy number polymorphism in the human genome. Science 2004, 305:525–528.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA, 30322, USA

    Christa Lese Martin

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  1. Christa Lese Martin
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  2. David H. Ledbetter
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Correspondence to Christa Lese Martin.

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Martin, C.L., Ledbetter, D.H. Autism and cytogenetic abnormalities: Solving autism one chromosome at a time. Curr Psychiatry Rep 9, 141–147 (2007). https://doi.org/10.1007/s11920-007-0084-9

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  • DOI: https://doi.org/10.1007/s11920-007-0084-9

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