Copy number variation of LINGO1 in familial dystonic tremor

Vafa Alakbarzade; Thomas Iype; Barry A. Chioza; Royana Singh; Gaurav V. Harlalka; Holly Hardy; Ajith Sreekantan-Nair; Christos Proukakis; Kathryn Peall; Lorraine N. Clark; Richard Caswell; Hana Lango Allen; Matthew Wakeling; John K. Chilton; Emma L. Baple; Elan D. Louis; Thomas T. Warner; Andrew H. Crosby

doi:10.1212/NXG.0000000000000307

Copy number variation of LINGO1 in familial dystonic tremor

Vafa Alakbarzade, Thomas Iype, Barry A. Chioza, Royana Singh, Gaurav V. Harlalka, Holly Hardy, Ajith Sreekantan-Nair, Christos Proukakis, Kathryn Peall, Lorraine N. Clark, Richard Caswell, Hana Lango Allen, Matthew Wakeling, John K. Chilton, Emma L. Baple, Elan D. Louis, Thomas T. Warner, Andrew H. Crosby

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Objective To elucidate the genetic cause of a large 5 generation South Indian family with multiple individuals with predominantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor. Methods Whole-genome single nucleotide polymorphism (SNP) microarray analysis was undertaken to look for copy number variants in the affected individuals. Results Whole-genome SNP microarray studies identified a tandem duplicated genomic segment of chromosome 15q24 present in all affected family members. Whole-genome sequencing demonstrated that it comprised a ∼550-kb tandem duplication encompassing the entire LINGO1 gene. Conclusions The identification of a genomic duplication as the likely molecular cause of this condition, resulting in an additional LINGO1 gene copy in affected cases, adds further support for a causal role of this gene in tremor disorders and implicates increased expression levels of LINGO1 as a potential pathogenic mechanism.

Original language	English (US)
Article number	e307
Journal	Neurology: Genetics
Volume	5
Issue number	1
DOIs	https://doi.org/10.1212/NXG.0000000000000307
State	Published - Feb 1 2019
Externally published	Yes

ASJC Scopus subject areas

Clinical Neurology
Genetics(clinical)

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Alakbarzade, V., Iype, T., Chioza, B. A., Singh, R., Harlalka, G. V., Hardy, H., Sreekantan-Nair, A., Proukakis, C., Peall, K., Clark, L. N., Caswell, R., Lango Allen, H., Wakeling, M., Chilton, J. K., Baple, E. L., Louis, E. D., Warner, T. T., & Crosby, A. H. (2019). Copy number variation of LINGO1 in familial dystonic tremor. Neurology: Genetics, 5(1), Article e307. https://doi.org/10.1212/NXG.0000000000000307

Alakbarzade, V, Iype, T, Chioza, BA, Singh, R, Harlalka, GV, Hardy, H, Sreekantan-Nair, A, Proukakis, C, Peall, K, Clark, LN, Caswell, R, Lango Allen, H, Wakeling, M, Chilton, JK, Baple, EL, Louis, ED, Warner, TT & Crosby, AH 2019, 'Copy number variation of LINGO1 in familial dystonic tremor', Neurology: Genetics, vol. 5, no. 1, e307. https://doi.org/10.1212/NXG.0000000000000307

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title = "Copy number variation of LINGO1 in familial dystonic tremor",

abstract = "Objective To elucidate the genetic cause of a large 5 generation South Indian family with multiple individuals with predominantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor. Methods Whole-genome single nucleotide polymorphism (SNP) microarray analysis was undertaken to look for copy number variants in the affected individuals. Results Whole-genome SNP microarray studies identified a tandem duplicated genomic segment of chromosome 15q24 present in all affected family members. Whole-genome sequencing demonstrated that it comprised a ∼550-kb tandem duplication encompassing the entire LINGO1 gene. Conclusions The identification of a genomic duplication as the likely molecular cause of this condition, resulting in an additional LINGO1 gene copy in affected cases, adds further support for a causal role of this gene in tremor disorders and implicates increased expression levels of LINGO1 as a potential pathogenic mechanism.",

author = "Vafa Alakbarzade and Thomas Iype and Chioza, {Barry A.} and Royana Singh and Harlalka, {Gaurav V.} and Holly Hardy and Ajith Sreekantan-Nair and Christos Proukakis and Kathryn Peall and Clark, {Lorraine N.} and Richard Caswell and {Lango Allen}, Hana and Matthew Wakeling and Chilton, {John K.} and Baple, {Emma L.} and Louis, {Elan D.} and Warner, {Thomas T.} and Crosby, {Andrew H.}",

note = "Funding Information: The authors would like to thank the family described herein for participating in this study. The study was supported by the Medical Research Council (G1002279, G1001931), Newlife Foundation for Disabled Children, and Reta Lila Weston Medical Trust. Publisher Copyright: {\textcopyright} American Academy of Neurology.",

year = "2019",

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doi = "10.1212/NXG.0000000000000307",

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T1 - Copy number variation of LINGO1 in familial dystonic tremor

AU - Alakbarzade, Vafa

AU - Iype, Thomas

AU - Chioza, Barry A.

AU - Singh, Royana

AU - Harlalka, Gaurav V.

AU - Hardy, Holly

AU - Sreekantan-Nair, Ajith

AU - Proukakis, Christos

AU - Peall, Kathryn

AU - Clark, Lorraine N.

AU - Caswell, Richard

AU - Lango Allen, Hana

AU - Wakeling, Matthew

AU - Chilton, John K.

AU - Baple, Emma L.

AU - Louis, Elan D.

AU - Warner, Thomas T.

AU - Crosby, Andrew H.

N1 - Funding Information: The authors would like to thank the family described herein for participating in this study. The study was supported by the Medical Research Council (G1002279, G1001931), Newlife Foundation for Disabled Children, and Reta Lila Weston Medical Trust. Publisher Copyright: © American Academy of Neurology.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Objective To elucidate the genetic cause of a large 5 generation South Indian family with multiple individuals with predominantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor. Methods Whole-genome single nucleotide polymorphism (SNP) microarray analysis was undertaken to look for copy number variants in the affected individuals. Results Whole-genome SNP microarray studies identified a tandem duplicated genomic segment of chromosome 15q24 present in all affected family members. Whole-genome sequencing demonstrated that it comprised a ∼550-kb tandem duplication encompassing the entire LINGO1 gene. Conclusions The identification of a genomic duplication as the likely molecular cause of this condition, resulting in an additional LINGO1 gene copy in affected cases, adds further support for a causal role of this gene in tremor disorders and implicates increased expression levels of LINGO1 as a potential pathogenic mechanism.

AB - Objective To elucidate the genetic cause of a large 5 generation South Indian family with multiple individuals with predominantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor. Methods Whole-genome single nucleotide polymorphism (SNP) microarray analysis was undertaken to look for copy number variants in the affected individuals. Results Whole-genome SNP microarray studies identified a tandem duplicated genomic segment of chromosome 15q24 present in all affected family members. Whole-genome sequencing demonstrated that it comprised a ∼550-kb tandem duplication encompassing the entire LINGO1 gene. Conclusions The identification of a genomic duplication as the likely molecular cause of this condition, resulting in an additional LINGO1 gene copy in affected cases, adds further support for a causal role of this gene in tremor disorders and implicates increased expression levels of LINGO1 as a potential pathogenic mechanism.

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Copy number variation of LINGO1 in familial dystonic tremor

Abstract

ASJC Scopus subject areas

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