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

Birgitte Bertelsen; Linea Melchior; Lars R Jensen; Camilla Groth; Birte Glenthøj; Renata Rizzo; Nanette Mol Debes; Liselotte Skov; Karen Brøndum-Nielsen; Peristera Paschou; Asli Silahtaroglu; Zeynep Tümer

doi:10.1038/ejhg.2014.24

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

Birgitte Bertelsen, Linea Melchior, Lars R Jensen, Camilla Groth, Birte Glenthøj, Renata Rizzo, Nanette Mol Debes, Liselotte Skov, Karen Brøndum-Nielsen, Peristera Paschou, Asli Silahtaroglu, Zeynep Tümer

43 Citations (Scopus)

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.

Original language	English
Journal	European Journal of Human Genetics
Volume	22
Issue number	11
Pages (from-to)	1283-1289
Number of pages	7
ISSN	1018-4813
DOIs	https://doi.org/10.1038/ejhg.2014.24
Publication status	Published - 5 Nov 2014

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ejhg.2014.24

http://www.nature.com/ejhg/journal/vaop/ncurrent/full/ejhg201424a.html

Cite this

Bertelsen, B., Melchior, L., Jensen, L. R., Groth, C., Glenthøj, B., Rizzo, R., Debes, N. M., Skov, L., Brøndum-Nielsen, K., Paschou, P., Silahtaroglu, A., & Tümer, Z. (2014). Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome. European Journal of Human Genetics, 22(11), 1283-1289. https://doi.org/10.1038/ejhg.2014.24

Bertelsen, B, Melchior, L, Jensen, LR, Groth, C, Glenthøj, B, Rizzo, R, Debes, NM, Skov, L, Brøndum-Nielsen, K, Paschou, P, Silahtaroglu, A & Tümer, Z 2014, 'Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome', European Journal of Human Genetics, vol. 22, no. 11, pp. 1283-1289. https://doi.org/10.1038/ejhg.2014.24

@article{138e1b041791493ab6cc29419acdcc13,

title = "Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome",

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.",

author = "Birgitte Bertelsen and Linea Melchior and Jensen, {Lars R} and Camilla Groth and Birte Glenth{\o}j and Renata Rizzo and Debes, {Nanette Mol} and Liselotte Skov and Karen Br{\o}ndum-Nielsen and Peristera Paschou and Asli Silahtaroglu and Zeynep T{\"u}mer",

year = "2014",

month = nov,

day = "5",

doi = "10.1038/ejhg.2014.24",

language = "English",

volume = "22",

pages = "1283--1289",

journal = "European Journal of Human Genetics",

issn = "1018-4813",

publisher = "nature publishing group",

number = "11",

}

TY - JOUR

T1 - Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome

AU - Bertelsen, Birgitte

AU - Melchior, Linea

AU - Jensen, Lars R

AU - Groth, Camilla

AU - Glenthøj, Birte

AU - Rizzo, Renata

AU - Debes, Nanette Mol

AU - Skov, Liselotte

AU - Brøndum-Nielsen, Karen

AU - Paschou, Peristera

AU - Silahtaroglu, Asli

AU - Tümer, Zeynep

PY - 2014/11/5

Y1 - 2014/11/5

N2 - 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.

AB - 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.

U2 - 10.1038/ejhg.2014.24

DO - 10.1038/ejhg.2014.24

M3 - Journal article

C2 - 24549057

SN - 1018-4813

VL - 22

SP - 1283

EP - 1289

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 11

ER -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this