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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Case-Control Studies
  • Chromosomes, Human, Pair 7 / genetics
  • DNA Copy Number Variations
  • Denmark
  • Endopeptidases / genetics*
  • Exons
  • Female
  • Gene Deletion*
  • Gene Rearrangement
  • Genetic Predisposition to Disease
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice
  • Microarray Analysis
  • Obsessive-Compulsive Disorder / genetics
  • Sequence Analysis, DNA
  • Tics / genetics
  • Tourette Syndrome / genetics*
  • White People / genetics

Substances

  • Endopeptidases
  • IMMP2L protein, human