NOTCH2NLC GGC Repeat Expansions Are Associated with Sporadic Essential Tremor: Variable Disease Expressivity on Long-Term Follow-up

Adeline S.L. Ng; Weng Khong Lim; Zheyu Xu; Helen L. Ong; Yi Jayne Tan; Wei Ying Sim; Ebonne Y.L. Ng; Jing Xian Teo; Jia Nee Foo; Tchoyoson C.C. Lim; Wai Yung Yu; Ling Ling Chan; Hwei Yee Lee; Zhiyong Chen; Ee Wei Lim; Simon K.S. Ting; Kumar M. Prakash; Louis C.S. Tan; Zhao Yi; Eng King Tan

doi:10.1002/ana.25803

NOTCH2NLC GGC Repeat Expansions Are Associated with Sporadic Essential Tremor: Variable Disease Expressivity on Long-Term Follow-up

Adeline S.L. Ng, Weng Khong Lim, Zheyu Xu, Helen L. Ong, Yi Jayne Tan, Wei Ying Sim, Ebonne Y.L. Ng, Jing Xian Teo, Jia Nee Foo, Tchoyoson C.C. Lim, Wai Yung Yu, Ling Ling Chan, Hwei Yee Lee, Zhiyong Chen, Ee Wei Lim, Simon K.S. Ting, Kumar M. Prakash, Louis C.S. Tan, Zhao Yi, Eng King Tan^*

^*Corresponding author for this work

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

43 Citations (Scopus)

Abstract

We screened 662 subjects comprising 462 essential tremor (ET) subjects (285 sporadic, 125 with family history, and 52 probands from well-characterized ET pedigrees) and 200 controls and identified pathogenic NOTCH2NLC GGC repeat expansions in 4 sporadic ET patients. Two patients were followed up for >1 decade; one with 90 repeats remained an ET phenotype that did not evolve after 40 years, whereas another patient with 107 repeats developed motor symptoms and cognitive impairment after 8 to 10 years. Neuroimaging in this patient revealed severe leukoencephalopathy; diffusion-weighted imaging hyperintensity in the corticomedullary junction and skin biopsy revealed intranuclear inclusions suggestive of intranuclear inclusion body disease (NIID). No GGC repeats of >60 units were detected in familial ET cases and controls, although 4 ET patients carried 47 to 53 “intermediate” repeats. NOTCH2NLC GGC repeat expansions can be associated with sporadic ET. Carriers presenting with a pure ET phenotype may or may not convert to NIID up to 4 decades after initial tremor onset. ANN NEUROL 2020;88:614–618.

Original language	English
Pages (from-to)	614-618
Number of pages	5
Journal	Annals of Neurology
Volume	88
Issue number	3
DOIs	https://doi.org/10.1002/ana.25803
Publication status	Published - Sept 1 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020 American Neurological Association

ASJC Scopus Subject Areas

Neurology
Clinical Neurology

Access to Document

10.1002/ana.25803

Cite this

Ng, A. S. L., Lim, W. K., Xu, Z., Ong, H. L., Tan, Y. J., Sim, W. Y., Ng, E. Y. L., Teo, J. X., Foo, J. N., Lim, T. C. C., Yu, W. Y., Chan, L. L., Lee, H. Y., Chen, Z., Lim, E. W., Ting, S. K. S., Prakash, K. M., Tan, L. C. S., Yi, Z., & Tan, E. K. (2020). NOTCH2NLC GGC Repeat Expansions Are Associated with Sporadic Essential Tremor: Variable Disease Expressivity on Long-Term Follow-up. Annals of Neurology, 88(3), 614-618. https://doi.org/10.1002/ana.25803

@article{f7ad6c4ce6a94d60a0504f258c5b758a,

title = "NOTCH2NLC GGC Repeat Expansions Are Associated with Sporadic Essential Tremor: Variable Disease Expressivity on Long-Term Follow-up",

abstract = "We screened 662 subjects comprising 462 essential tremor (ET) subjects (285 sporadic, 125 with family history, and 52 probands from well-characterized ET pedigrees) and 200 controls and identified pathogenic NOTCH2NLC GGC repeat expansions in 4 sporadic ET patients. Two patients were followed up for >1 decade; one with 90 repeats remained an ET phenotype that did not evolve after 40 years, whereas another patient with 107 repeats developed motor symptoms and cognitive impairment after 8 to 10 years. Neuroimaging in this patient revealed severe leukoencephalopathy; diffusion-weighted imaging hyperintensity in the corticomedullary junction and skin biopsy revealed intranuclear inclusions suggestive of intranuclear inclusion body disease (NIID). No GGC repeats of >60 units were detected in familial ET cases and controls, although 4 ET patients carried 47 to 53 “intermediate” repeats. NOTCH2NLC GGC repeat expansions can be associated with sporadic ET. Carriers presenting with a pure ET phenotype may or may not convert to NIID up to 4 decades after initial tremor onset. ANN NEUROL 2020;88:614–618.",

author = "Ng, {Adeline S.L.} and Lim, {Weng Khong} and Zheyu Xu and Ong, {Helen L.} and Tan, {Yi Jayne} and Sim, {Wei Ying} and Ng, {Ebonne Y.L.} and Teo, {Jing Xian} and Foo, {Jia Nee} and Lim, {Tchoyoson C.C.} and Yu, {Wai Yung} and Chan, {Ling Ling} and Lee, {Hwei Yee} and Zhiyong Chen and Lim, {Ee Wei} and Ting, {Simon K.S.} and Prakash, {Kumar M.} and Tan, {Louis C.S.} and Zhao Yi and Tan, {Eng King}",

note = "Publisher Copyright: {\textcopyright} 2020 American Neurological Association",

year = "2020",

month = sep,

day = "1",

doi = "10.1002/ana.25803",

language = "English",

volume = "88",

pages = "614--618",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

number = "3",

}

Ng, ASL, Lim, WK, Xu, Z, Ong, HL, Tan, YJ, Sim, WY, Ng, EYL, Teo, JX, Foo, JN, Lim, TCC, Yu, WY, Chan, LL, Lee, HY, Chen, Z, Lim, EW, Ting, SKS, Prakash, KM, Tan, LCS, Yi, Z & Tan, EK 2020, 'NOTCH2NLC GGC Repeat Expansions Are Associated with Sporadic Essential Tremor: Variable Disease Expressivity on Long-Term Follow-up', Annals of Neurology, vol. 88, no. 3, pp. 614-618. https://doi.org/10.1002/ana.25803

TY - JOUR

T1 - NOTCH2NLC GGC Repeat Expansions Are Associated with Sporadic Essential Tremor

T2 - Variable Disease Expressivity on Long-Term Follow-up

AU - Ng, Adeline S.L.

AU - Lim, Weng Khong

AU - Xu, Zheyu

AU - Ong, Helen L.

AU - Tan, Yi Jayne

AU - Sim, Wei Ying

AU - Ng, Ebonne Y.L.

AU - Teo, Jing Xian

AU - Foo, Jia Nee

AU - Lim, Tchoyoson C.C.

AU - Yu, Wai Yung

AU - Chan, Ling Ling

AU - Lee, Hwei Yee

AU - Chen, Zhiyong

AU - Lim, Ee Wei

AU - Ting, Simon K.S.

AU - Prakash, Kumar M.

AU - Tan, Louis C.S.

AU - Yi, Zhao

AU - Tan, Eng King

PY - 2020/9/1

Y1 - 2020/9/1

N2 - We screened 662 subjects comprising 462 essential tremor (ET) subjects (285 sporadic, 125 with family history, and 52 probands from well-characterized ET pedigrees) and 200 controls and identified pathogenic NOTCH2NLC GGC repeat expansions in 4 sporadic ET patients. Two patients were followed up for >1 decade; one with 90 repeats remained an ET phenotype that did not evolve after 40 years, whereas another patient with 107 repeats developed motor symptoms and cognitive impairment after 8 to 10 years. Neuroimaging in this patient revealed severe leukoencephalopathy; diffusion-weighted imaging hyperintensity in the corticomedullary junction and skin biopsy revealed intranuclear inclusions suggestive of intranuclear inclusion body disease (NIID). No GGC repeats of >60 units were detected in familial ET cases and controls, although 4 ET patients carried 47 to 53 “intermediate” repeats. NOTCH2NLC GGC repeat expansions can be associated with sporadic ET. Carriers presenting with a pure ET phenotype may or may not convert to NIID up to 4 decades after initial tremor onset. ANN NEUROL 2020;88:614–618.

AB - We screened 662 subjects comprising 462 essential tremor (ET) subjects (285 sporadic, 125 with family history, and 52 probands from well-characterized ET pedigrees) and 200 controls and identified pathogenic NOTCH2NLC GGC repeat expansions in 4 sporadic ET patients. Two patients were followed up for >1 decade; one with 90 repeats remained an ET phenotype that did not evolve after 40 years, whereas another patient with 107 repeats developed motor symptoms and cognitive impairment after 8 to 10 years. Neuroimaging in this patient revealed severe leukoencephalopathy; diffusion-weighted imaging hyperintensity in the corticomedullary junction and skin biopsy revealed intranuclear inclusions suggestive of intranuclear inclusion body disease (NIID). No GGC repeats of >60 units were detected in familial ET cases and controls, although 4 ET patients carried 47 to 53 “intermediate” repeats. NOTCH2NLC GGC repeat expansions can be associated with sporadic ET. Carriers presenting with a pure ET phenotype may or may not convert to NIID up to 4 decades after initial tremor onset. ANN NEUROL 2020;88:614–618.

UR - http://www.scopus.com/inward/record.url?scp=85088154208&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85088154208&partnerID=8YFLogxK

U2 - 10.1002/ana.25803

DO - 10.1002/ana.25803

M3 - Article

C2 - 32495371

AN - SCOPUS:85088154208

SN - 0364-5134

VL - 88

SP - 614

EP - 618

JO - Annals of Neurology

JF - Annals of Neurology

IS - 3

ER -

NOTCH2NLC GGC Repeat Expansions Are Associated with Sporadic Essential Tremor: Variable Disease Expressivity on Long-Term Follow-up

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Access to Document

Other files and links

Fingerprint

Cite this