The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease

Raquel Duran; Niccolo E. Mencacci; Aikaterini V. Angeli; Maryam Shoai; Emma Deas; Henry Houlden; Atul Mehta; Derralynn Hughes; Timothy M. Cox; Patrick Deegan; Anthony H. Schapira; Andrew J. Lees; Patricia Limousin; Paul R. Jarman; Kailash P. Bhatia; Nicholas W. Wood; John Hardy; Tom Foltynie

doi:10.1002/mds.25248

The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease

Raquel Duran, Niccolo E. Mencacci, Aikaterini V. Angeli, Maryam Shoai, Emma Deas, Henry Houlden, Atul Mehta, Derralynn Hughes, Timothy M. Cox, Patrick Deegan, Anthony H. Schapira, Andrew J. Lees, Patricia Limousin, Paul R. Jarman, Kailash P. Bhatia, Nicholas W. Wood, John Hardy^*, Tom Foltynie

^*Corresponding author for this work

Neurology

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

112 Scopus citations

Abstract

Background: Heterozygous loss-of-function mutations in the acid beta-glucocerebrosidase (GBA1) gene, responsible for the recessive lysosomal storage disorder, Gaucher's disease (GD), are the strongest known risk factor for Parkinson's disease (PD). Our aim was to assess the contribution of GBA1 mutations in a series of early-onset PD. Methods: One hundred and eighty-five PD patients (with an onset age of ≤50) and 283 age-matched controls were screened for GBA1 mutations by Sanger sequencing. Results: We show that the frequency of GBA1 mutations is much higher in this patient series than in typical late-onset patient cohorts. Furthermore, our results reveal that the most prevalent PD-associated GBA1 mutation is E326K, a variant that does not, when homozygous, cause GD. Conclusions: Our results confirm recent reports that the mutation, E326K, predisposes to PD and suggest that, in addition to reduced GBA1 activity, other molecular mechanisms may contribute to the development of the disease.

Original language	English (US)
Pages (from-to)	232-236
Number of pages	5
Journal	Movement Disorders
Volume	28
Issue number	2
DOIs	https://doi.org/10.1002/mds.25248
State	Published - Feb 2013

Funding

Keywords

E326K
Early onset
GBA
Gaucher's disease
Parkinson's disease

ASJC Scopus subject areas

Clinical Neurology
Neurology

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10.1002/mds.25248

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Duran, R., Mencacci, N. E., Angeli, A. V., Shoai, M., Deas, E., Houlden, H., Mehta, A., Hughes, D., Cox, T. M., Deegan, P., Schapira, A. H., Lees, A. J., Limousin, P., Jarman, P. R., Bhatia, K. P., Wood, N. W., Hardy, J., & Foltynie, T. (2013). The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease. Movement Disorders, 28(2), 232-236. https://doi.org/10.1002/mds.25248

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title = "The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease",

abstract = "Background: Heterozygous loss-of-function mutations in the acid beta-glucocerebrosidase (GBA1) gene, responsible for the recessive lysosomal storage disorder, Gaucher's disease (GD), are the strongest known risk factor for Parkinson's disease (PD). Our aim was to assess the contribution of GBA1 mutations in a series of early-onset PD. Methods: One hundred and eighty-five PD patients (with an onset age of ≤50) and 283 age-matched controls were screened for GBA1 mutations by Sanger sequencing. Results: We show that the frequency of GBA1 mutations is much higher in this patient series than in typical late-onset patient cohorts. Furthermore, our results reveal that the most prevalent PD-associated GBA1 mutation is E326K, a variant that does not, when homozygous, cause GD. Conclusions: Our results confirm recent reports that the mutation, E326K, predisposes to PD and suggest that, in addition to reduced GBA1 activity, other molecular mechanisms may contribute to the development of the disease.",

keywords = "E326K, Early onset, GBA, Gaucher's disease, Parkinson's disease",

author = "Raquel Duran and Mencacci, {Niccolo E.} and Angeli, {Aikaterini V.} and Maryam Shoai and Emma Deas and Henry Houlden and Atul Mehta and Derralynn Hughes and Cox, {Timothy M.} and Patrick Deegan and Schapira, {Anthony H.} and Lees, {Andrew J.} and Patricia Limousin and Jarman, {Paul R.} and Bhatia, {Kailash P.} and Wood, {Nicholas W.} and John Hardy and Tom Foltynie",

year = "2013",

month = feb,

doi = "10.1002/mds.25248",

language = "English (US)",

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pages = "232--236",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "John Wiley and Sons Inc.",

number = "2",

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Duran, R, Mencacci, NE, Angeli, AV, Shoai, M, Deas, E, Houlden, H, Mehta, A, Hughes, D, Cox, TM, Deegan, P, Schapira, AH, Lees, AJ, Limousin, P, Jarman, PR, Bhatia, KP, Wood, NW, Hardy, J & Foltynie, T 2013, 'The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease', Movement Disorders, vol. 28, no. 2, pp. 232-236. https://doi.org/10.1002/mds.25248

TY - JOUR

T1 - The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease

AU - Duran, Raquel

AU - Mencacci, Niccolo E.

AU - Angeli, Aikaterini V.

AU - Shoai, Maryam

AU - Deas, Emma

AU - Houlden, Henry

AU - Mehta, Atul

AU - Hughes, Derralynn

AU - Cox, Timothy M.

AU - Deegan, Patrick

AU - Schapira, Anthony H.

AU - Lees, Andrew J.

AU - Limousin, Patricia

AU - Jarman, Paul R.

AU - Bhatia, Kailash P.

AU - Wood, Nicholas W.

AU - Hardy, John

AU - Foltynie, Tom

PY - 2013/2

Y1 - 2013/2

N2 - Background: Heterozygous loss-of-function mutations in the acid beta-glucocerebrosidase (GBA1) gene, responsible for the recessive lysosomal storage disorder, Gaucher's disease (GD), are the strongest known risk factor for Parkinson's disease (PD). Our aim was to assess the contribution of GBA1 mutations in a series of early-onset PD. Methods: One hundred and eighty-five PD patients (with an onset age of ≤50) and 283 age-matched controls were screened for GBA1 mutations by Sanger sequencing. Results: We show that the frequency of GBA1 mutations is much higher in this patient series than in typical late-onset patient cohorts. Furthermore, our results reveal that the most prevalent PD-associated GBA1 mutation is E326K, a variant that does not, when homozygous, cause GD. Conclusions: Our results confirm recent reports that the mutation, E326K, predisposes to PD and suggest that, in addition to reduced GBA1 activity, other molecular mechanisms may contribute to the development of the disease.

AB - Background: Heterozygous loss-of-function mutations in the acid beta-glucocerebrosidase (GBA1) gene, responsible for the recessive lysosomal storage disorder, Gaucher's disease (GD), are the strongest known risk factor for Parkinson's disease (PD). Our aim was to assess the contribution of GBA1 mutations in a series of early-onset PD. Methods: One hundred and eighty-five PD patients (with an onset age of ≤50) and 283 age-matched controls were screened for GBA1 mutations by Sanger sequencing. Results: We show that the frequency of GBA1 mutations is much higher in this patient series than in typical late-onset patient cohorts. Furthermore, our results reveal that the most prevalent PD-associated GBA1 mutation is E326K, a variant that does not, when homozygous, cause GD. Conclusions: Our results confirm recent reports that the mutation, E326K, predisposes to PD and suggest that, in addition to reduced GBA1 activity, other molecular mechanisms may contribute to the development of the disease.

KW - E326K

KW - Early onset

KW - GBA

KW - Gaucher's disease

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JF - Movement Disorders

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ER -

The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease

Abstract

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Keywords

ASJC Scopus subject areas

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