Catecholaminergic neurotransmission is widely studied in ADHD and has yielded several candidate genes conferring a small amount of risk, suggesting a potential role for additional neurotransmitter systems. We found a maternally derived GRM5 CNV in three siblings. Both GRM5 and GRM7 (above) belong to the glutamatergic receptor gene family hypothesized to play a role in ADHD.43, 44, 45 The GRM5 variant, a hemizygous deletion of 82 kb (11 SNPs; Supplementary Figure S2), showed uniparental inheritance and was experimentally validated by FISH (Figure 1). Neuropsychiatric assessment indicated that all three children in this family, one 18-year-old male and two females with ages 15 and 11, met the criteria for ADHD with significant impairment since early childhood. All three children showed some improvement in symptoms with medications but persistent overall dysfunction in academic, social and behavioral spheres in spite of superior IQ levels. Assessment of the mother using the ADHD Self-Report Scale indicated a likelihood of ADHD (scores of 20 for part A and 12 for part B).46 The mother, and to a lesser extent, all three children, display problems with spatial
