Tourette syndrome is a neurodevelopmental disorder characterized by multiple motor and vocal tics, and the disorder is often accompanied by comorbidities such as attention-deficit hyperactivity-disorder and obsessive compulsive disorder. Tourette syndrome has a complex etiology, but the underlying environmental and genetic factors are largely unknown. IMMP2L (inner mitochondrial membrane peptidase, subunit 2) located on chromosome 7q31 is one of the genes suggested as a susceptibility factor in disease pathogenesis. Through screening of a Danish cohort comprising 188 unrelated Tourette syndrome patients for copy number variations, we identified seven patients with intragenic IMMP2L deletions (3.7%), and this frequency was significantly higher (P=0.0447) compared with a Danish control cohort (0.9%). Four of the seven deletions identified did not include any known exons of IMMP2L, but were within intron 3. These deletions were found to affect a shorter IMMP2L mRNA species with two alternative 5'-exons (one including the ATG start codon). We showed that both transcripts (long and short) were expressed in several brain regions, with a particularly high expression in cerebellum and hippocampus. The current findings give further evidence for the role of IMMP2L as a susceptibility factor in Tourette syndrome and suggest that intronic changes in disease susceptibility genes should be investigated further for presence of alternatively spliced exons.European Journal of Human Genetics advance online publication, 19 February 2014; doi:10.1038/ejhg.2014.24.
European Journal of Human Genetics, 2014, Vol 22, Issue 11, p. 1283-1289
Animals; Attention Deficit Disorder with Hyperactivity; Case-Control Studies; Chromosomes, Human, Pair 7; DNA Copy Number Variations; Denmark; Endopeptidases; European Continental Ancestry Group; Exons; Female; Gene Deletion; Gene Rearrangement; Genetic Predisposition to Disease; Humans; In Situ Hybridization, Fluorescence; Male; Mice; Microarray Analysis; Obsessive-Compulsive Disorder; Sequence Analysis, DNA; Tics; Tourette Syndrome; Journal Article; Research Support, Non-U.S. Gov't