In the 12/16 patients for whom we did not identify homozygous candidate mutations, we examined the mutational spectrum under different models of inheritance. Out of an average of 696 rare, heterozygous, and potentially deleterious variants per exome, we identified 67 candidate compound heterozygous changes (at least two deleterious variants in the same gene). Sequenom genotyping validated an average of 27 of these variants, and phasing of the resulting set in trios revealed ∼4 true compound heterozygotes with one allele inherited from each parent. Genotyping of unaffected siblings when available reduced this number to ∼2 variants per individual consistent with fully penetrant, recessive disease (Table S4). For three patients, we narrowed down the candidates to 1 gene and for 8 patients there were no candidate genes with compound heterozygous variants (Table S5). Analysis of X-linked mutations did not identify mutations in well-validated X-linked autism genes, though 11/14 male patients carried rare hemizygous X-linked variants, three of which occurred in genes associated with intellectual disability (ARHGEF6, AFF2, and OCRL). The first variant in ARHGEF6, which encodes Rac/Cdc42 guanine nucleotide exchange factor 6,
