Skip to main content
SpringerLink
Log in

Genetic Studies in Autism

  • Review Article
  • Published:
The Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Autism is a complex neurodevelopmental disorder, which has captured the attention of not only pediatricians but also the parents. From the symptoms until the final diagnosis, parents undergo a diagnostic odyssey that involves a battery of tests without much yield. This has led to an increase in the referrals to the clinical geneticists to rule out the possible genetic etiology that can have implications for the parents for future pregnancy. This chapter focuses on the various genetic causes and their appropriate application in the evaluation of a child with Autism Spectrum Disorders (ASDs).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Santangelo SL, Tsatsanis K. What is known about autism: genes, brain, and behavior. Am J Pharmacogenomics. 2005;5:71–92.

    Article  CAS  PubMed  Google Scholar 

  2. Baio J. Prevalence of autism spectrum disorders - autism and developmental disabilities monitoring network, 14 sites, United States,2008. Centers Dis Contr Prev. 2012;61:1–19.

    Google Scholar 

  3. Juneja M, Mishra D, Russell PS, et al; INCLEN Study Group. INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD): development and validation. Indian Pediatr. 2014;51:359–65.

    Article  PubMed  Google Scholar 

  4. Newschaffer CJ, Croen LA, Daniels J, et al. The epidemiology of autism spectrum disorders. Annu Rev Public Health. 2007;28:235–58.

    Article  PubMed  Google Scholar 

  5. Hallmayer J, Cleveland S, Torres A, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry. 2011;68:1095–102.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Levy D, Ronemus M, Yamrom B, et al. Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron. 2011;70:886–97.

    Article  CAS  PubMed  Google Scholar 

  7. Betancur C. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res. 2011;1380:42–77.

    Article  CAS  PubMed  Google Scholar 

  8. Volkmar FR, Nelson DS. Seizure disorders in autism. J Am Acad Child Adolesc Psychiatry. 1990;29:127–9.

    Article  CAS  PubMed  Google Scholar 

  9. Daniels AM, Halladay AK, Shih A, Elder LM, Dawson G. Approaches to enhancing the early detection of autism spectrum disorders: a systemic review of the literature. J Am Acad Child Adolesc Psychiatry. 2014;53:141–52.

    Article  PubMed  Google Scholar 

  10. Shi L, Zhang X, Golhar R, et al. Whole-genome sequencing in an autism multiplex family. Mol Autism. 2013;4:8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Reddy KS. Cytogenetic abnormalities and fragile-X syndrome in autism spectrum disorder. BMC Med Genet. 2005;6:3.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Devlin B, Scherer SW. Genetic architecture in autism spectrum disorder. Curr Opin Genet Dev. 2012;22:229–37.

    Article  CAS  PubMed  Google Scholar 

  13. Depienne C, Moreno-De-Luca D, Heron D, et al. Screening for genomic rearrangements and methylation abnormalities of the 15q11-q13 region in autism spectrum disorders. Biol Psychiatry. 2009;66:349–59.

    Article  CAS  PubMed  Google Scholar 

  14. Schaefer GB, Starr L, Pickering D, Skar G, Dehaai K, Sanger WG. Array comparative genomic hybridization findings in a cohort referred for an autism evaluation. J Child Neurol. 2010;25:1498–503.

    Article  PubMed  Google Scholar 

  15. Shinawi M, Liu P, Kang S-H, et al. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. J Med Genet. 47: 332–41.

  16. Sanders SJ, Murtha MT, Gupta AR, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012;485:237–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Johnson HM, Gaitanis J, Morrow EM. Genetics in autism diagnosis: adding molecular subtypes to neurobehavioral diagnoses. Med Health R I. 2011;94:124–6.

    PubMed  PubMed Central  Google Scholar 

  18. Manning M, Hudgins L. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med. 2010;12:742–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Poultney CS, Goldberg AP, Drapeau E, et al. Identification of small exonic CNV from whole exome sequence data and application to autism spectrum disorder. Am J Hum Gene. 2013;93:607–19.

    Article  CAS  Google Scholar 

  20. Chahrour M, Zoghbi HY. The story of Rett syndrome: from clinic to neurobiology. Neuron. 2007;56:422–37.

    Article  CAS  PubMed  Google Scholar 

  21. O'Roak BJ, Deriziotis P, Lee C, et al. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat Genet. 2011;43:585–9.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Cukier HN, Dueker ND, Slifer SH, et al. Exome Sequencing of Extended Families with Autism Reveals Genes Shared Across Neurodevelopmental and Neuropsychiatric Disorders. Mol Autism. 2014;5:1.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Bi C, Wu J, Jiang T, et al. Mutations of ANK3 identified by exome sequencing are associated with autism susceptibility. Hum Mutat. 2012;33:1635–8.

    Article  CAS  PubMed  Google Scholar 

  24. Neale B, Kou Y, Liu L, et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature. 2012;485:242–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. O’Roak BJ, Vives L, Girirajan S, et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature. 2012;485:246–50.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Baieli S, Pavone L, Meli C, Fiumara A, Coleman M. Autism and phenylketonuria. J Autism Dev Disord. 2003;33:201–4.

    Article  PubMed  Google Scholar 

  27. Schaefer GB, Mendelsohn NJ; Professional Practice and Guidelines Committee. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med. 2013;15:399–407..

  28. Frye RE. Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder. Epilepsy Behav. 2015;47:147–57.

    Article  PubMed  Google Scholar 

  29. Skaar DA, Shao Y, Haines JL, et al. Analysis of the RELN gene as a genetic risk factor for autism. Mol Psychiatry. 2005;10:563–71.

    Article  CAS  PubMed  Google Scholar 

  30. Leblond CS, Heinrich J, Delorme R, et al. Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. PLoS Genet. 2012;8:e1002521.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kumar RA, KaraMohamed S, Sudi J, et al. Recurrent 16p11.2 microdeletions in autism. Hum Mol Genet. 2008;17:628–38.

    Article  CAS  PubMed  Google Scholar 

  32. Sutcliffe JS, Delahanty RJ, Prasad HC, et al. Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors. Am J Hum Genet. 2005;77:265–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Guo T, McDonald-McGinn D, Blonska A, et al. Genotype and cardiovascular phenotype correlations with TBX1 in 1,022 velo-cardio- facial/DiGeorge/22q11.2 deletion syndrome patients. Hum Mutat. 2011;32:1278–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Schaefer GB, Lutz RE. Diagnostic yield in the clinical genetic evaluation of autism spectrum disorders. Genet Med. 2006;8:549–56.

    PubMed  Google Scholar 

  35. Clifford S, Dissanayake C, Bui QM, Huggins R, Taylor AK, Loesch DZ. Autism spectrum phenotype in males and females with fragile X full mutation and premutation. J Autism Dev Disord. 2007;37:738–47.

    Article  PubMed  Google Scholar 

  36. Lam CW, Yeung WL, Ko CH, et al. Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. J Med Genet. 2000;37:E41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. McBride KL, Varga EA, Pastore MT, et al. Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly. Autism Res. 2010;3:137–41.

    Article  PubMed  Google Scholar 

  38. Guo X, Tu WJ, Shi XD. Tuberous sclerosis complex in autism. Iran J Pediatr. 2012;22:408–11.

    PubMed  PubMed Central  Google Scholar 

  39. Buxbaum JD, Cai G, Nygren G, et al. Mutation analysis of the NSD1 gene in patients with autism spectrum disorders and macrocephaly. BMC Med Genet. 2007;8:68.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Mamidala MP, Polinedi A, P T V PK, et al. Prenatal, perinatal and neonatal risk factors of Autism Spectrum Disorder: a comprehensive epidemiological assessment from India. Res Dev Disabil. 2013;34:3004–13.

    Article  PubMed  Google Scholar 

  41. Guhathakurta S, Singh AS, Sinha S, et al. Analysis of serotonin receptor 2A gene (HTR2A): association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes. Neurochem Int. 2009;55:754–9.

    Article  CAS  PubMed  Google Scholar 

  42. Naushad SM, Jain JM, Prasad CK, Naik U, Akella RR. Autistic children exhibit distinct plasma amino acid profile. Indian J Biochem Biophys. 2013;50:474–8.

    CAS  PubMed  Google Scholar 

  43. Verma D, Chakraborti B, Karmakar A, et al. Sexual dimorphic effect in the genetic association of monoamine oxidase a (MAOA) markers with autism spectrum disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2014;50:11–20.

    Article  CAS  Google Scholar 

  44. Schaefer GB, Mendelsohn NJ. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med. 2013;15:399–407.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge Dr. Rashmi Shukla, Mr. Pankaj and Dr Madhumita Roy Chaudhary for providing karyotype, array, MLPA pictures respectively. They also thank Dr. Shivaram for his inputs.

Contributions

SS: Wrote the first draft of manuscript and corrections as per comments; NG: Contributed the major part including the outline of the article, the flow diagram, important clinical cases and other major inputs; MK: Provided important intellectual comments and will act as guarantor for the paper.

Author information

Authors and Affiliations

  1. Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India

    Shruthi Sudarshan, Neerja Gupta & Madhulika Kabra

Authors
  1. Shruthi Sudarshan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neerja Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Madhulika Kabra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neerja Gupta.

Ethics declarations

Conflict of Interest

None.

Source of Funding

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sudarshan, S., Gupta, N. & Kabra, M. Genetic Studies in Autism. Indian J Pediatr 83, 1133–1140 (2016). https://doi.org/10.1007/s12098-015-1989-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-015-1989-7

Keywords

Search

Navigation