Analysis of four DLX homeobox genes in autistic probands.
BACKGROUND
Linkage studies in autism have identified susceptibility loci on chromosomes 2q and 7q, regions containing the DLX1/2 and DLX5/6 bigene clusters. The DLX genes encode homeodomain transcription factors that control craniofacial patterning and differentiation and survival of forebrain inhibitory neurons. We investigated the role that sequence variants in DLX genes play in autism by in-depth resequencing of these genes in 161 autism probands from the AGRE collection.


RESULTS
Sequencing of exons, exon/intron boundaries and known enhancers of DLX1, 2, 5 and 6 identified several nonsynonymous variants in DLX2 and DLX5 and a variant in a DLX5/6 intragenic enhancer. The nonsynonymous variants were detected in 4 of 95 families from which samples were sequenced. Two of these four SNPs were not observed in 378 undiagnosed samples from North American populations, while the remaining 2 were seen in one sample each.


CONCLUSIONS
Segregation of these variants in pedigrees did not generally support a contribution to autism susceptibility by these genes, although functional analyses may provide insight into the biological understanding of these important proteins.
Hamilton
Steven P
SP
Department of Psychiatry, University of California, San Francisco, CA, USA. steveh@lppi.ucsf.edu
Woo
Jonathan M
JM
Carlson
Elaine J
EJ
Ghanem
Nöel
N
Ekker
Marc
M
Rubenstein
John L R
JL
D001321:Autistic Disorder / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005091:Exons; D005192:Family Health; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D018398:Homeodomain Proteins / Q000235:genetics*; D040582:Inheritance Patterns; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors