Gene Linked to Language Disorder and Autism
A respite from the sad chain of questionable studies on autism is provided by this week's NEJM.
Investigators from the UK and UCLA report their discovery of 9 DNA variations (ie, single-nucleotide polymorphisms, or SNPs) in specific regions of the CNTNAP2 gene,* which are associated with a particular language impairment in nonautistic children of families affected by language disorders. These SNPs were found to associate in a highly significant way with the heritable behavioral marker (or endophenotype) of nonsense-word repetition.
But what's really interesting is that these SNP regions in CNTNAP2 have also been implicated (by some of the same investigators) in language delays among children with autism (Alarcon et al. Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am J Hum Genet. 2008;82:150-159).
The NEJM authors conclude that similar DNA variations in these regions of the CNTNAP2 gene may predispose individuals to isolated language impairment, or they may contribute to the language impairment in autistic spectrum disorder. In the case of autism, other behavioral features, like impaired social interactions or repetitive behaviors (ie, stereotypy) are proposed to be caused by different genetic mechanisms.
These findings support the prevailing idea that autism, and the observed spectrum of the disorder, is the clinical manifestation of more than one complex, genetic alteration (see Happe F et al. Time to give up on a single explanation for autism. Nat Neurosci. 2006;9:1218-1220).
* CNTNAP2 encodes CASPR2, a neurexin, which is expressed in the developing human cortex. The authors identified CNTNAP2 as a target of the transcription factor FOXP2. (FOXP2 downregulates CNTNAP2 expression.) Mutations in FOXP2 are associated with speech and language disorders.
