While the major emphasis over the last decade has been on the contribution of common genetic variations (>5% of the population), several recent findings highlight the importance of studying rare, highly penetrant variants, including the identification of mutations in the gene Slit and trk like family member 1 (SLITRK1) (19) and mapping of rare chromosomal abnormalities disrupting the Contactin-associated protein-like 2 (CNTNAP2) (20) and Neuroligin 4 (NLGN4) (21) genes, with these latter two also strongly implicated in autism spectrum disorders (ASD). Most recently, we characterized a highly penetrant mutation in the gene L-histidine Decarboxylase (HDC) in a dense TS pedigree, implicating histaminergic (HA) neurotransmission in the genesis or modulation of tics (22).
