autism
Autism is a common and genetically heterogeneous disorder, with an estimated heritability of >90%.
Its specific underlying causes are largely unknown. Here, I propose that low levels of autistic vulnerability, reflected in social-cognitive processing differences, do not necessarily manifest in a behavioural phenotype but are usually compensated for during development.
They are more likely to lead to a recognizable syndrome among individuals of low intelligence, who are male or have independent neurodevelopmental vulnerability owing to a wide range of gene mutations, chromosomal anomalies or environmental insults.
Consequently, the apparent association between mental retardation and autistic syndromes is not because they usually have common causes, but rather because the presence of both features greatly increases the probability of clinical ascertainment.
Susceptibility loci
1q21-22
3q25-27 (12192642)
7q
15q11-q13 (12567325)
17q11 (in males) (15467983)
17q21 (15806440, 15877280)
GABA receptor subunit genes
GLO1 variants
Reviews
Skuse DH. Rethinking the nature of genetic vulnerability to autistic spectrum disorders. Trends Genet. 2007 Aug;23(8):387-95. PMID: 17630015
Thornalley PJ. Unease on the role of glyoxalase 1 in high-anxiety-related behaviour. Trends Mol Med. 2006 May;12(5):195-9. PMID: 16616641
Folstein SE, Rosen-Sheidley B. Genetics of autism: complex aetiology for a heterogeneous disorder. Nat Rev Genet. 2001 Dec;2(12):943-55. PMID: 11733747
Lamb JA, Moore J, Bailey A, Monaco AP. Autism: recent molecular genetic advances. Hum Mol Genet. 2000 Apr 12;9(6):861-8. PMID: 10767308
References
Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, Shago M, Moessner R, Pinto D, Ren Y, Thiruvahindrapduram B, Fiebig A, Schreiber S, Friedman J, Ketelaars CE, Vos YJ, Ficicioglu C, Kirkpatrick S, Nicolson R, Sloman L, Summers A, Gibbons CA, Teebi A, Chitayat D, Weksberg R, Thompson A, Vardy C, Crosbie V, Luscombe S, Baatjes R, Zwaigenbaum L, Roberts W, Fernandez B, Szatmari P, Scherer SW. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet. 2008 Feb;82(2):477-88. PMID: 18252227
Jacquemont ML, Sanlaville D, Redon R, Raoul O, Cormier-Daire V, Lyonnet S, Amiel J, Le Merrer M, Heron D, de Blois MC, Prieur M, Vekemans M, Carter NP, Munnich A, Colleaux L, Philippe A. Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders. J Med Genet. 2006 Nov;43(11):843-9. PMID: 16840569