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Abstract
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.
GLOSSARY
- AJ=
- Ashkenazi Jewish;
- ANOVA=
- analysis of variance;
- CI=
- confidence interval;
- GCase=
- glucocerebrosidase;
- OR=
- odds ratio;
- PD=
- Parkinson disease;
- SMase=
- sphingomyelin phosphodiesterase
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 1544
Supplemental data at www.neurology.org
- Received July 20, 2012.
- Accepted in final form December 10, 2012.
- © 2013 American Academy of Neurology
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- Re:The p.L302P mutation of lysosomal enzyme gene SMPD1 is rare in Taiwanese Parkinson's disease
- The p.L302P mutation of lysosomal enzyme gene SMPD1 is rare in Taiwanese Parkinson's disease
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