In:
Neurology Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 6 ( 2020-12), p. e523-
Kurzfassung:
To provide a variant-specific estimate of incidence, penetrance, sex distribution, and association with dementia of the 4 most common Parkinson disease (PD)-associated GBA variants, we analyzed a large cohort of 4,923 Italian unrelated patients with primary degenerative parkinsonism (including 3,832 PD) enrolled in a single tertiary care center and 7,757 ethnically matched controls. Methods The p.E326K, p.T369M, p.N370S, and p.L444P variants were screened using an allele-specific multiplexed PCR approach. All statistical procedures were performed using R or Plink v1.07. Results Among the 4 analyzed variants, the p.L444P confirmed to be the most strongly associated with disease risk for PD, PD dementia (PDD), and dementia with Lewy bodies (DLB) (odds ratio [OR] for PD 15.63, 95% confidence interval [CI] = 8.04–30.37, p = 4.97*10 −16 ; OR for PDD 29.57, 95% CI = 14.07–62.13, p = 3.86*10 −19 ; OR for DLB 102.7, 95% CI = 31.38–336.1, p = 1.91*10 −14 ). However, an unexpectedly high risk for dementia was conferred by p.E326K (OR for PDD 4.80, 95% CI = 2.87–8.02, p = 2.12*10 −9 ; OR for DLB 12.24, 95% CI = 4.95–30.24, p = 5.71*10 −8 ), which, on the basis of the impact on glucocerebrosidase activity, would be expected to be mild. The 1.5–2:1 male sex bias described in sporadic PD was lost in p.T369M carriers. We also showed that PD penetrance for p.L444P could reach the 15% at age 75 years. Conclusions We report a large monocentric study on GBA -PD assessing mutation-specific data on the sex distribution, penetrance, incidence, and association with dementia of the 4 most frequent deleterious variants in GBA .
Materialart:
Online-Ressource
ISSN:
2376-7839
DOI:
10.1212/NXG.0000000000000523
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2020
ZDB Id:
2818607-2
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