• Ilda Patrícia Ribeiro Department of Biology, Universidade do Minho
  • Manuela Freitas Department of Genetics, INSA, Centro de Genética Médica Doutor Jacinto Magalhães
  • Natália Oliva-Teles Department of Genetics, INSA, Centro de Genética Médica Doutor Jacinto Magalhães



Autism spectrum disorders, Autism, Chromosome, Locus, Gene


Autism spectrum disorders (ASD) are neurodevelopmental disorders that include behaviour, communicational and social interaction impairments. According to DSM-IV TR there are five ASDs in the category of pervasive developmental disorders: autistic disorder, Asperger Syndrome, pervasive developmental disorder not otherwise specified, childhood disintegrative disorder, and Rett syndrome. The prevalence of ASD varies from 10 per 10000 to 60 cases per 10 000 children, according to different epidemiological studies. A small number of individuals with ASD has a well defined aetiology, being this challenging for scientific purposes. Studies of twins and families have showed a high heritability of autistic disorder, nonetheless its genetic bases, as well as the identification of some genes or proteins that can be use to identify these disorders have not been completely clarified. According to the literature only a small percentage of subjects with ASDs have know aetiology, which has raised concern in the scientific community in the last decade. The ASDs have been associated with known genetic causes in 10-15% of the cases. Different genes and chromosomal regions (loci) potentially associated with ASDs have been described, being the chromosomal anomalies responsible for less than 10% of the autism cases. There are also some cytogenetic abnormalities in patients with autism described in the literature, namely the duplication of 15q11-q13, the deletion and duplication in the 16p11 band, and the deletion in the 22q13 region. The chromosomal regions are reviewed in detail in the present article, as it is our conviction that future research will clarify some of the complex genetic basis of ASDs. The cytogenetic anomalies of the locus 15q11-q13 are present in 1 -4% of the autism patients; it is reasonable to establish an association between the microdeletion in the sub-band 16p11.2 and the autism, and, in addition, the deletion and duplication in the chromosome 22q13.3 are potential risk factors to the ASDs.


Download data is not yet available.


Abrahams BS, Geschwind DH. Advances in autism genetics:

on the threshold of a new neurobiology. Nat Rev Genet

;9:341 -55.

Alarcon M, Cantor RM, Liu J, Gilliam TC, Geschwind DH.

Evidence for a language quantitative trait locus on chromosome

q in multiplex autism families. Am J Hum Genet

;70:60 -71.

Chakrabarti S, Fombonne E. Pervasive developmental disorders

in preschool children: conÞ rmation of high prevalence.

Am J Psychiatry 2005;162:1133 -41.

Yeargin -Allsopp M, Rice C, Karapurkar T, Doernberg N, Boyle

C, Murphy C. Prevalence of autism in a US metropolitan area.

JAMA 2003; 289:49 -55.

Oliveira G, Ataíde A, Marques C, Miguel TS, Coutinho AM,

Mota -Vieira L, et al. Epidemiology of autism spectrum disorder

in Portugal: prevalence, clinical characterization, and medical

conditions. Dev Med Child Neurol 2007;49:726 -33.

Volkmar FR, Szatmari P, Sparrow SS. Sex differences in

pervasive developmental disorders. J Autism Dev Disord

;23:579 -91.

American Psychiatric Association. Diagnostic and Statistical

Manual of Mental Disorders, Fourth Edition, Text Revision.

Washington, DC: American Psychiatric Association, 2000.

Kanner L. Autistic disturbances of affective contact. Nervous

Child 1943; 2:217 -250.

Nurmi EL, Bradford Y, Chen Y, Hall J, Arnone B, Gardiner MB,

et al. Linkage disequilibrium at the Angelman syndrome gene

UBE3A in autism families. Genomics 2001;77:105 -13.

Reddy KS. Cytogenetic abnormalities and fragile -X syndrome

in Autism Spectrum Disorder. BMC Med Genet 2005;6:3.

Casanova MF, Buxhoeveden DP, Cohen M, Switala AE,

Roy EL. Minicolumnar pathology in dyslexia. Ann Neurol

;52:108 -10.

Courchesne E, Karns CM, Davis HR, Ziccardi R, Carper RA,

Tigue ZD, et al. Unusual brain growth patterns in early life

in patients with autistic disorder: an MRI study. Neurology

;57:245 -54.

Sparks BF, Friedman SD, Shaw DW, Aylward EH, Echelard D,

Artru AA, et al. Brain structural abnormalities in young children

with autism spectrum disorder. Neurology 2002;59:184 -92.

Amir RE, Van den Veyver IB, Wan M., Tran CQ, Francke U,

Zoghbi HY. Rett syndrome is caused by mutations in X -linked

MECP2, encoding methyl -CpG -binding protein 2. Nat Genet

;23:185 -8.

Manzi B, PorÞ rio MC, Pennacchia S, Galasso C, Curatolo

P. Molecular Genetics of Autism. Int J Ch Neuropsychiatry

;2:103 -9.

Geschwind DH, Levitt P. Autism spectrum disorders: developmental

disconnection syndromes. Curr Opin Neurobiol

;17:103 -11.

Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E,

Yuzda E, et al. Autism as a strongly genetic disorder: evidence

from a British twin study. Psychol Med 1995;25:63 -77.

Levy SE, Mandell DS, Schultz RT. Autism. Lancet

;374:1627 -38.

Folstein SE, Rosen -Sheidley B. Genetics of autism: complex

aetiology for a heterogeneous disorder. Nat Rev Genet

;2:943 -55.

Gillberg C. Chromosomal disorders and autism. J Autism Dev

Disord 1998;28:415 -25.

Kumar RA, Christian SL. Genetics of autism spectrum disorders.

Curr Neurol Neurosci Rep 2009;9:188 -97.

Veenstra -VanderWeele J, Christian SL, Cook ED Jr. Autism

as a paradigmatic complex genetic disorder. Annu Rev Genomics

Human Genet 2004;5:379 -405.

Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan

R, et al. Functional impact of global rare copy number variation

in autism spectrum disorders. Nature 2010;466:368 -72.

Vorstman JA, Staal WG, van Daalen E, van Engeland H,

Hochstenbach PF, Franke L. IdentiÞ cation of novel autism

candidate regions through analysis of reported cytogenetic

abnormalities associated with autism. Mol Psychiatry 2006;

:18 -28.

International Molecular Genetic Study of Autism Consortium.

A full genome screen for autism with evidence for

linkage to a region on chromosome 7q. Hum Mol Genet

;7:571 -8.

Bonati MT, Russo S, Finelli P, Valsecchi MR, Cogliati F, Cavalleri

F, et al. Evaluation of autism traits in Angelman syndrome:

a resource to unfold autism genes. Neurogenetics

;8:169 -78.

Owens DF, Kriegstein AR. Is there more to GABA than synaptic

inhibition? Nat Rev Neurosci 2002;3:715 -27.

Collins AL, Ma D, Whitehead PL, Martin ER., Wright HH,

Abramson RK, et al. Investigation of autism and GABA receptor

subunit genes in multiple ethnic groups. Neurogenetics

;7:167 -74.

Ma DQ, Whitehead PL, Menold MM, Martin ER, Ashley -Koch

AE, Mei H, et al. IdentiÞ cation of signiÞ cant association and

gene -gene interaction of GABA receptor subunit genes in autism.

Am J Hum Genet 2005; 77:377 -88.

DeLorey TM, Olsen RW. GABA and epileptogenesis: comparing

gabrb3 gene -deÞ cient mice with Angelman syndrome in

man. Epilepsy Res 1999;36:123 -32.

Rougeulle C, Glatt H, Lalande M. The Angelman syndrome

candidate gene, UBE3A/E6 -AP, is imprinted in brain. Nat Genet

;17:14 -5.

Ben -Shachar S, Lanpher B, German JR, Qasaymeh M, Potocki

L, Nagamani SC, et al. Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation,

and psychiatric disorders. J Med Genet 2009;46:382 -8.

Rosenfeld JA, Coppinger J, Bejjani B, Girirajan S, Eichler EE,

Shaffer LG, et al. Speech delays and behavioral problems are

the predominant features in individuals with developmental

delays and 16p11.2 microdeletions and microduplications. J

Neurodevelop Disord 2010;2:26 -38.

Weiss LA, Shen Y, Korn JM, Arking DE, Miller DT, Fossdal R,

et al. Association between microdeletion and microduplication

at 16p11.2 and autism. N Engl J Med 2008;358:667 -75.

Horev G, Ellegood J, Lerch JP, Son Y -EE, Muthuswamy L,

Vogel H, et al. Dosage -dependent phenotypes in models of

p11.2 lesions found in autism. Proc Natl Acad Sci USA

;108:17076 -81.

Heilstedt HA, Ballif BC, Howard LA, Kashork CD, Shaffer

LG. Population data suggest that deletions of 1p36 are a

relatively common chromosome abnormality. Clin Genet

;64:310 -6.

Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste

P, Fauchereau F, et al. Mutations in the gene encoding the

synaptic scaffolding protein SHANK3 are associated with autism

spectrum disorders. Nat Genet 2007;39:25 -7.

Freitag CM, Staal W, Klauck SM, Duketis E, Waltes R. Genetics

of autistic disorders: review and clinical implications. Eur

Child Adolesc Psychiatry 2010; 19:169 -78.

Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood

S, et al. Autism genome -wide copy number variation reveals

ubiquitin and neuronal genes. Nature 2009;459:569 -73.



How to Cite

Ribeiro IP, Freitas M, Oliva-Teles N. AUTISM SPECTRUM DISORDERS – ADVANCES IN MOLECULAR BIOLOGY. REVNEC [Internet]. 2017Aug.22 [cited 2023Oct.2];22(1):19-24. Available from:



Review Articles

Most read articles by the same author(s)