A t(3;9)(q25.1;q34.3) translocation leading to OLFM1 fusion transcripts in Gilles de la Tourette syndrome, OCD and ADHD

作者：Bertelsen Birgitte; Melchior Linea; Jensen Lars Riff; Groth Camilla; Nazaryan Lusine; Debes Nanette Mol; Skov Liselotte; Xie Gangcai; Sun Wei; Brondum Nielsen Karen; Kuss Andreas Walter; Chen Wei; Tumer Zeynep^*

来源：Psychiatry Research, 2015, 225(3): 268-275.

DOI：10.1016/j.psychres.2014.12.028

• Tourette syndrome
• Microscopically balanced translocation
• Fusion transcripts
• OLFM1
• Neuropsychiatric disorder

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.

• 出版日期2015-2
• 单位河北医科大学