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, results in an I444N mutation. The second variant in AFF2, encoding Fragile X mental retardation 2, causes a P847A mutation that is predicted to be benign by PolyPhen-2. The third variant disrupts a splice donor site in OCRL (oculocerebrorenal syndrome of Lowe gene) (Table S6). Splicing mutations in OCRL have been identified in patients with Lowe oculocerebrorenal syndrome [33]–[36], characterized by hydrophthalmia, cataract, intellectual disability, vitamin D-resistant rickets, amino aciduria, and reduced ammonia production by the kidney. Since patient AU1019301 is not known to exhibit a renal phenotype or any other Lowe syndrome phenotypes, it is unlikely that this mutation is causative of the neurological condition of the patient. Segregation analysis showed that these three X-linked mutations were inherited from heterozygous mothers, confirming that they are not cell line artifacts. Since our study design enriched for families with potential shared inheritance, it does not permit confident determination of the causative nature of these potential compound heterozygous or X-linked mutations, which
