Autism-lessons from the X chromosome.
Recognized cases of autism spectrum disorders are on the rise. It is unclear whether this increase is attributable to secular trends in biological susceptibility, or to a change in diagnostic practices and recognition. One hint concerning etiological influences is the universally reported male excess (in the range of 4:1 to 10:1). Evidence suggests that genetic influences from the X chromosome play a crucial role in engendering this male vulnerability. In this review, we discuss three categories of genetic disease that highlight the importance of X-linked genes in the manifestation of an autistic phenotype: aneuploides (Turner syndrome and Klinefelter syndrome), trinucleotide expansions (Fragile X syndrome) and nucleotide mutations (Rett Syndrome, Neuroligins 3 & 4, and SLC6A8). The lessons from these diseases include an understanding of autistic features as a broad phenotype rather than as a single clinical entity, the role of multiple genes either alone or in concert with the manifestation of autistic features, and the role of epigenetic factors such as imprinting and X-inactivation in the expression of disease severity. Better understanding of the clinical phenotypes of social cognition and the molecular neurogenetics of X-linked gene disorders will certainly provide additional tools for understanding autism in the years to come.
Marco
Elysa J
EJ
Behavioral and Brain Sciences Unit, Institute of Child Health, London, UK.
Skuse
David H
DH
D001321:Autistic Disorder / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D011596:Psychomotor Disorders / Q000453:epidemiology / Q000235:genetics; D012730:Sex Chromosomes / Q000235:genetics; D012737:Sex Factors; D013577:Syndrome
C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2