Two genes, PTPRD and GRM5, were especially intriguing as putative candidate genes for ADHD. Hemizygous deletions involving the protein tyrosine phosphatase gene, PTPRD, were detected in four unrelated ADHD probands, spanning exon 2, exons 3–9, exon 9 and intron 2 of the gene, respectively (Supplementary Figure S1). PTPRD CNVs were experimentally validated by quantitative PCR in two probands (Supplementary Table S4). The deletion was confirmed by q-PCR in both probands as well as in a transmitting parent for the one case where DNA was available (130-386-1). Two of the four ADHD probands with PTPRD deletions reported symptoms consistent with restless legs syndrome (RLS), which shares high rates of bidirectional comorbidity as well as dopaminergic dysfunction with ADHD.33, 34 Intriguingly, a recent genome-wide association study has implicated PTPRD as a locus for RLS.35 Moreover, genetic variants of PTPRD associate with bronchial asthma,36 which is reported to occur at higher rates in children with ADHD,37 and RLS patients have been shown to have increased use of asthma medications.38 Studies of the PTPRD gene in mice show high expression in the hippocampus, the
