Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Greece

Kalinderi, Kallirhoe; Bostantjopoulou, Sevasti; Paisán-Ruı́z, Coro; Katsarou, Zoe; Hardy, John; Fidani, Liana

doi:10.1016/j.neulet.2009.01.029

Cited by 87 publications

(61 citation statements)

References 17 publications

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“…One study ever screened the GBA gene and reported the mutation frequency of 5.7% in 88 Canadian PD patients [21]. We GBA mutation frequency of 0.91% in our controls is also equivalent to that of 0.4% and 1.0% reported in other Caucasian populations [7,8,10,22,23].…”

Section: Discussionsupporting

confidence: 81%

Mutations in the glucocerebrosidase gene are common in patients with Parkinson's disease from Eastern Canada

Han

Grimes

et al. 2015

International Journal of Neuroscience

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Section: Discussionsupporting

confidence: 81%

Mutations in the glucocerebrosidase gene are common in patients with Parkinson's disease from Eastern Canada

Han

Grimes

et al. 2015

International Journal of Neuroscience

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“…Following reports of parkinsonism in GD1 patients and their heterozygote family members,(Goker-Alpan et al 2004) PD populations were screened for GBA1 mutations. Full mutation screening revealed that 4–9 % of PD patients in Asian and Northern European populations were heterozygous for GBA1 mutations (Mitsui et al 2009; Ziegler et al 2007; Bras et al 2009; Kalinderi et al 2009; Sidransky et al 2009). A large meta-analysis found that PD patients had a five-fold increased risk of carrying a GBA1 mutation compared to non-PD controls (Sidransky et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Greater risk of parkinsonism associated with non‐N370S GBA1 mutations

Barrett

Giraldo

Capablo

et al. 2012

J of Inher Metab Disea

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Mutations in β-glucosidase (GBA1) are the most common genetic risk factor for Parkinson disease (PD). There is evidence to suggest that PD risk is greater (1) in GBA1 heterozygotes with non-N370S GBA1 mutations compared to N370S mutations and (2) in GD type 1 (GD1) patients compared to GBA1 heterozygotes. This study aimed to determine the comparative risk of parkin-sonism in individuals who are affected or carriers of Gaucher disease (GD) and to ascertain the influence of different GBA1 mutations on risk/clinical expression. We conducted a secondary analysis of cross-sectional data assessing the prevalence of parkinsonism in a population of GD1 patients and their heterozygote and non-carrier family members. Two logistic regression models, both employing a family-specific random effect, were used to assess (1) the association between GBA1 mutation (N370S or non-N370S) and parkinsonism among GBA1 heterozygotes and (2) the association between GBA1 genotype and parkinsonism. Parkinsonism was present in 8.6 % of GD1 (7/81), 8.7 % of GBA1 heterozygotes (18/207), and 2.2 % of non-carriers (1/45). For those greater than 60 years old, parkinsonism was present in 38.5 % (5/13) of GD1 (5/13), 15.3 % of GBA1 heterozygotes (13/85), and 7.1 % of non-carriers (1/14). Among GBA1 heterozygotes, non-N370S mutations were associated with a significantly increased risk of parkinsonism compared to N370S (OR=22.5; p=0.035; 95%CI: 1.24, 411). In this population, each additional GBA1 mutation was associated with a non-significant two-fold increased risk of parkinsonism. GBA1 heterozygotes with non-N370S mutations associated with Gaucher disease have an increased risk of parkinsonism compared to those with N370S mutations.

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“…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.…”

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confidence: 99%

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

et al. 2013

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Objective: To study the possible association of founder mutations in the lysosomal storage disorder genes HEXA, SMPD1, and MCOLN1 (causing Tay-Sachs, Niemann-Pick A, and mucolipidosis type IV diseases, respectively) with Parkinson disease (PD).Methods: Two PD patient cohorts of Ashkenazi Jewish (AJ) ancestry, that included a total of 938 patients, were studied: a cohort of 654 patients from Tel Aviv, and a replication cohort of 284 patients from New York. Eight AJ founder mutations in the HEXA, SMPD1, and MCOLN1 genes were analyzed. The frequencies of these mutations were compared to AJ control groups that included large published groups undergoing prenatal screening and 282 individuals matched for age and sex.Results: Mutation frequencies were similar in the 2 groups of patients with PD. The SMPD1 p.L302P was strongly associated with a highly increased risk for PD (odds ratio 9.4, 95% confidence interval 3.9-22.8, p , 0.0001), as 9/938 patients with PD were carriers of this mutation compared to only 11/10,709 controls. Conclusions:The SMPD1 p.L302P mutation is a novel risk factor for PD. Although it is rare on a population level, the identification of this mutation as a strong risk factor for PD may further elucidate PD pathogenesis and the role of lysosomal pathways in disease development.

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Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Greece

Cited by 87 publications

References 17 publications

Mutations in the glucocerebrosidase gene are common in patients with Parkinson's disease from Eastern Canada

Mutations in the glucocerebrosidase gene are common in patients with Parkinson's disease from Eastern Canada

Greater risk of parkinsonism associated with non‐N370S GBA1 mutations

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

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