Abstract
Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder with a strong genetic etiology; however, finding of candidate genes is hampered by its genetic heterogeneity and the influence of non-genetic factors on disease pathogenesis. We report a case of a male patient with GTS, obsessive compulsive disorder, attention-deficit/hyperactivity-disorder, as well as other comorbidities, and a translocation t(3;9)(q25.1;q34.3) inherited from a mother with tics. Mate-pair sequencing revealed that the translocation breakpoints truncated the olfactomedin 1 (OLFM1) gene and two uncharacterized transcripts. Reverse-transcription PCR identified several fusion transcripts in the carriers, and OLFM1 expression was found to be high in GTS-related human brain regions. As OLFM1 plays a role in neuronal development it is a likely candidate gene for neuropsychiatric disorders and haploinsufficiency of OLFM1 could be a contributing risk factor to the phenotype of the carriers. In addition, one of the fusion transcripts may exert a dominant-negative or gain-of-function effect. OLFM1 is unlikely to be a major GTS susceptibility gene as no point mutations or copy number variants affecting OLFM1 were identified in 175 additional patients. The translocation described is thus a unique event, but further studies in larger cohorts are required to elucidate involvement of OLFM1 in GTS pathogenesis.
| Original language | English |
|---|---|
| Journal | Psychiatry Research |
| Volume | 225 |
| Issue number | 3 |
| Pages (from-to) | 268-75 |
| Number of pages | 8 |
| ISSN | 0165-1781 |
| DOIs | |
| Publication status | Published - 28 Feb 2015 |
Keywords
- Adult
- Attention Deficit Disorder with Hyperactivity
- Chromosomes, Human, Pair 3
- Chromosomes, Human, Pair 9
- Cohort Studies
- Comorbidity
- Denmark
- Extracellular Matrix Proteins
- Glycoproteins
- Humans
- Male
- Obsessive-Compulsive Disorder
- Point Mutation
- Tourette Syndrome
- Translocation, Genetic
- Young Adult
