found in the related NHE6 gene in a patient with an Angelman-like syndrome, which involves both autism symptoms and epilepsy (37). The NHE9 nonsense change here is carried by two male siblings with autistic disorder as well as their mother, who was reported to have had childhood language delay based on a parental language questionnaire (blind to genotype). One autistic son has electroencephalogram-confirmed epilepsy, and the second autistic son had two probable seizures but does not have known epilepsy. This nonsense change was not found in greater than 3800 control chromosomes. Complete resequencing of all exons and exon-intron boundaries in a greater than fivefold excess (480) of controls revealed no nonsense changes (table S6). Rare, nonconservative coding changes were more common in patients with autism with epilepsy compared with control subjects (5.95% versus 0.63%, Fisher’s exact test, P = 0.005 for total changes), although autistic patients without seizures did not differ significantly from controls in the rate of nonconservative changes (1.14% autism without seizures versus 0.63% controls). The heterozygous changes, in particular the nonsense mutation, likely affect gene dosage and suggest that the study of consanguineous pedigrees may identify genes of importance in nonconsanguineous populations as well.
