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Eur J Hum Genet. 2014 Nov;22(11):1283-9. doi: 10.1038/ejhg.2014.24. Epub 2014 Feb 19.

Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome.

Author information

1
Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
2
Institute for Human Genetics, Ernst-Moritz-Arndt-University Greifswald, Griefswald, Germany.
3
The Tourette Clinic, Department of Pediatrics, Herlev University Hospital, Herlev, Denmark.
4
Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Psychiatric Center Glostrup, Glostrup, Denmark.
5
Section of Child Neuropsychiatry, Department of Pediatrics, University of Catania, Catania, Italy.
6
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.
7
Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli, Greece.
8
Institute for Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.

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.

PMID:
24549057
PMCID:
PMC4200436
DOI:
10.1038/ejhg.2014.24
[Indexed for MEDLINE]
Free PMC Article
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