Research article

Analysis of four DLX homeobox genes in autistic probands

Steven P Hamilton^1,2 , Jonathan M Woo³ , Elaine J Carlson³ , Nöel Ghanem⁵ , Marc Ekker⁵ and John LR Rubenstein^1,4

¹  Department of Psychiatry, University of California, San Francisco, CA, USA

²  Center for Human Genetics, University of California, San Francisco, CA, USA

³  Genomics Core Facility, University of California, San Francisco, CA, USA

⁴  Nina Ireland Laboratory, University of California, San Francisco, CA, USA

⁵  Department of Biology, University of Ottawa, Ontario, Canada

author email corresponding author email

BMC Genetics 2005, 6:52doi:10.1186/1471-2156-6-52

Published:	2 November 2005

Abstract

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 DLX5/6intragenic 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.

Conclusion

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.