title: Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome.
abstract: 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.
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Bertelsen
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
authors.forename: Linea
authors.initials: L
authors.lastname: Melchior
authors.affiliation: Institute for Human Genetics, Ernst-Moritz-Arndt-University Greifswald, Griefswald, Germany.
authors.forename: Lars R
authors.initials: LR
authors.lastname: Jensen
authors.affiliation: The Tourette Clinic, Department of Pediatrics, Herlev University Hospital, Herlev, Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Groth
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Psychiatric Center Glostrup, Glostrup, Denmark.
authors.forename: Birte
authors.initials: B
authors.lastname: Glenthøj
authors.affiliation: Section of Child Neuropsychiatry, Department of Pediatrics, University of Catania, Catania, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Rizzo
authors.affiliation: The Tourette Clinic, Department of Pediatrics, Herlev University Hospital, Herlev, Denmark.
authors.forename: Nanette Mol
authors.initials: NM
authors.lastname: Debes
authors.affiliation: The Tourette Clinic, Department of Pediatrics, Herlev University Hospital, Herlev, Denmark.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Skov
authors.affiliation: 1] Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark [2] Institute for Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Brøndum-Nielsen
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli, Greece.
authors.forename: Peristera
authors.initials: P
authors.lastname: Paschou
authors.affiliation: Institute for Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Asli
authors.initials: A
authors.lastname: Silahtaroglu
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Tümer
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D016022:Case-Control Studies; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D056915:DNA Copy Number Variations; D003718:Denmark; D010450:Endopeptidases / Q000235:genetics*; D005091:Exons; D005260:Female; D017353:Gene Deletion; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D046228:Microarray Analysis; D009771:Obsessive-Compulsive Disorder / Q000235:genetics; D017422:Sequence Analysis, DNA; D020323:Tics / Q000235:genetics; D005879:Tourette Syndrome / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D010450:Endopeptidases; C425070:IMMP2L protein, human