We previously described a significant association between the HOXA1 G218 allele and increased head circumference in autism [Conciatori et al.(2004); Biol Psychiatry 55:413-419].
More direct tests, comparing genotype frequencies between probands and controls and tracking transmission of the A versus G alleles to affected offspring, did not support the contention that allele status for the HOXA1A218G polymorphism influences one's susceptibility to autism.
Therefore, although we cannot exclude the possibility that the samples in the two studies are intrinsically different, our data from our sample argue against a major role for HOXA1 (His)73(Arg) in liability to autism.
The results support a role for HOXA1 in susceptibility to autism, and add to the existing body of evidence implicating early brain stem injury in the etiology of ASDs.
Mice with null mutations of Hoxa1 or Hoxb1, two genes critical to hindbrain development, have phenotypic features frequently observed in autism, but no naturally occurring variants of either gene have been identified in mammals.