Evaluation of FOXP2 as an autism susceptibility gene.
A mutation in the gene FOXP2 was recently identified as being responsible for a complicated speech and language phenotype in a single large extended pedigree. This gene is of interest to autism because it lies in one of the most consistently linked autism chromosomal regions of interest. We therefore tested this gene for its involvement in autism in a large sample of autism families. We completely sequenced the exon containing the mutation, screened the remaining coding sequence using SSCP technology, and identified and genotyped two novel intronic tetranucleotide repeat polymorphisms that were then analyzed for evidence of linkage and linkage disequilibrium (LD). We identified two families in which heterozygous deletions of a small number of glutamines in a long poly-glutamine stretch were found in one parent and the autistic probands; no other non-conservative coding sequence changes were identified. Linkage and LD analyses were performed in 75 affected sibling pair families and in two subgroups of this sample defined by the presence/absence of severe language impairment. One allele appeared to have an opposite pattern of transmission in the language based subgroups, but otherwise the linkage and LD analyses were negative. We conclude that FOXP2 is unlikely to contribute significantly to autism susceptibility.
Department of Psychiatry, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. thomas-wassink@uiowa.edu
Thomas H
TH
Wassink
Joseph
J
Piven
Veronica J
VJ
Vieland
Jennifer
J
Pietila
Rhinda J
RJ
Goedken
Susan E
SE
Folstein
Val C
VC
Sheffield
D000483:Alleles; D001321:Autistic Disorder / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005190:Family; D005192:Family Health; D005260:Female; D051858:Forkhead Transcription Factors; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010455:Peptides / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion; D014157:Transcription Factors; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors; D010455:Peptides; D012097:Repressor Proteins; D014157:Transcription Factors; C097188:polyglutamine; D004247:DNA