Mutation screening of the dopamine D2 receptor gene in attention-deficit hyperactivity disorder subtypes: Preliminary report of a research strategy

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable syndrome with onset in childhood that is associated with clinical response to drugs, which increase the release of monoamines, especially dopamine. A variety of studies have reported on genetic associations of ADHD with polymorphisms for various component genes of the dopamine pathway. The promise of preliminary associations found with several genes is mitigated by the significant controversy that exists over what are the appropriate clinical characteristics of ADHD associated with its familial transmission. In the current report, we describe a strategy for mutation screening in common, complex disorders and its application to the systematic screening for coding region variation in the dopamine D2 receptor (DRD2) gene. We used groups of individuals who met diagnostic criteria for DSM-IV-defined ADHD subtypes, as well as recently defined latent class criteria for pure familial forms of ADHD. No coding region sequence variations were identified in the DRD2 gene that met our requirements for prevalence to be considered a candidate variant contributing to susceptibility for ADHD. (C) 2001 Wiley-Liss, Inc.