Glucocerebrosidase Mutations and Risk of Parkinson Disease in Chinese Patients

Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset

“…Furthermore, presence of a GBA variant was associated with an earlier onset of disease. Our results replicate the association of GBA with PD reported in other studies [10][11][12][13][14][15][16][17][18][19][20][21][22][23] ; however, we extend the association to include later onset patients with PD as well as familial disease.…”

“…23 In some studies, patients with PD harboring GBA variants had earlier age at disease onset. 12,15,19,21 Whether the discrepant results regarding the association of GBA with disease and age at onset result from true ethnic differences in GBA variant frequencies or from differences in the scope of the studies (i.e., only screening for certain variants as opposed to sequencing the entire coding region) remains to be determined.…”

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23] The goals of this study were to characterize sequence variation within GBA in a select subset of our large sample of patients with familial PD and then to test in the entire sample whether these sequence variants increased the risk for PD or were associated with an earlier onset of disease.…”

“…The remaining five variants had been previously reported in patients with PD and GD, as well as controls. 8,[10][11][12][13][14][15]17,[19][20][21] An unbiased estimate (using resampling techniques as described in Methods) of the frequency of the five previously reported GBA variants in the subset of the familial PD sample that met our strictest diagnostic criteria of verified PD was 12.6% and in the control sample was 5.3% (table 3). The mean age at onset of the patients with PD harboring a GBA variant was 56.8 years (median: 58, range: 30 -79).…”

The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease

“…Founder mutations in GBA can be detected in 1 out of 16 Ashkenazi Jews, and were shown to be important risk factors for Parkinson disease (PD) in this population 2,3 and in many other populations worldwide. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Three other lysosomal storage diseases that are caused by founder mutations can be found in the AJ population: Tay-Sachs disease 19 (carrier frequency of 1:27 20 ), Niemann-Pick disease type A 21 (1:115 20 ), and mucolipidosis type IV 22 (1:89 20 ). These 3 autosomal recessive diseases are caused by mutations in genes encoding lysosomal enzymes, 23 and their deficiency results in cellular accumulation of the enzymes' substrates.…”