Movement disorders : official journal of the Movement Disorder Society · 2012
The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease.
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Duran Raquel, Mencacci Niccolo E, Angeli Aikaterini V, Shoai Maryam, Deas Emma, Houlden Henry, Mehta Atul, Hughes Derralynn, Cox Timothy M, Deegan Patrick, Schapira Anthony H, Lees Andrew J, Limousin Patricia, Jarman Paul R, Bhatia Kailash P, Wood Nicholas W, Hardy John, Foltynie Tom
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAge of OnsetDNADatabases, GeneticExonsFemaleGaucher DiseaseGene FrequencyGlucosylceramidaseHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LeukocytesLewy Body DiseaseMaleMiddle AgedMolecular Sequence DataMutationOpen Reading FramesParkinson DiseaseProtein Serine-Threonine KinasesSequence Analysis, DNAUbiquitin-Protein LigasesUnited KingdomWhite PeopleYoung Adult