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

TY - JOUR

T1 - A t(3;9)(q25.1;q34.3) translocation leading to OLFM1 fusion transcripts in Gilles de la Tourette syndrome, OCD and ADHD

AU - Bertelsen, Birgitte

AU - Melchior, Linea

AU - Jensen, Lars Riff

AU - Groth, Camilla

AU - Nazaryan, Lusine

AU - Debes, Nanette Mol

AU - Skov, Liselotte

AU - Xie, Gangcai

AU - Sun, Wei

AU - Brøndum-Nielsen, Karen

AU - Kuss, Andreas Walter

AU - Chen, Wei

AU - Tümer, Zeynep

N1 - Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

PY - 2015/2/28

Y1 - 2015/2/28

N2 - 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.

AB - 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.

KW - Adult

KW - Attention Deficit Disorder with Hyperactivity

KW - Chromosomes, Human, Pair 3

KW - Chromosomes, Human, Pair 9

KW - Cohort Studies

KW - Comorbidity

KW - Denmark

KW - Extracellular Matrix Proteins

KW - Glycoproteins

KW - Humans

KW - Male

KW - Obsessive-Compulsive Disorder

KW - Point Mutation

KW - Tourette Syndrome

KW - Translocation, Genetic

KW - Young Adult

U2 - 10.1016/j.psychres.2014.12.028

DO - 10.1016/j.psychres.2014.12.028

M3 - Journal article

C2 - 25595337

SN - 0165-1781

VL - 225

SP - 268

EP - 275

JO - Psychiatry Research

JF - Psychiatry Research

IS - 3

ER -