Multiple genes are involved in the pathogenesis of autism. To study the causative gene, the relationship between autism endophenotypes and their closely related genes has been analyzed. There is a subgroup of autism spectrum disorder (ASD) in which the ratio of second digit length to fourth digit length (2D/4D) is low (short digit group, SDG). We studied the relationship between ASD and HOXD genes, which are located in the candidate locus for ASD and are associated with digit morphogenesis, with a particular focus on SDG. We analyzed 25 SNPs of HOXD11, HOXD12, and HOXD13 in the subject of 98 ASD, 89 healthy controls, and 16 non-autistic patients (non-ASD). There was no significant difference in the genotype frequencies between the ASD and the healthy controls. However, the G-112T heterozygote in the promoter region of HOXD11 was observed in only four patients with ASD and in none of the healthy controls or non-ASD subjects. Moreover, this HOXD11 G-112T was observed in three of 11 SDG with ASD but in none of the 15 non-SDG patients with ASD. There were eight SDG patients among the non-ASD ones, but this polymorphism was observed in none of them. Considering the above results, it is expected that candidate genes will be further identified, using HOXD11 G-112T polymorphism as a marker, by analyzing genes located near 2q in a larger number of ASD subjects with clinical signs of SDG.
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