Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson`s Disease

Background Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher`s disease, among patients with Parkinson`s disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson`s disease. Methods Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson`s disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel-Haenszel procedure used to estimate odds ratios across centers. Results All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of patients and 3% of controls, and among non-Ashkenazi Jewish subjects, either mutation was found in 3% of patients and less than 1% of controls. GBA was fully sequenced for 1883 non-Ashkenazi Jewish patients, and mutations were identified in 7%, showing that limited mutation screening can miss half the mutant alleles. The odds ratio for any GBA mutation in patients versus controls was 5.43 across centers. As compared with patients who did not carry a GBA mutation, those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were more likely to have atypical clinical manifestations. Conclusions Data collected from 16 centers demonstrate that there is a strong association between GBA mutations and Parkinson`s disease.

POSTMARITAL RESIDENCE PRACTICE IN SOUTHERN BRAZILIAN COASTAL GROUPS: CONTINUITY AND CHANGE

The coastal plains of the States of Parana and Santa Catarina, in Southern Brazil, were first settled around 6000 B.P. by shellmound builders, a successful fisher-hunter-gatherer population that inhabited the coastal lowlands practically unchanged for almost five thousand years. Shellmounds were typically occupied as residential sites as well as cemeteries, and are usually associated with rich alimentary zones. Around 1200 B.P., the first evidence of ceramics brought from the interior is found in coastal areas, and together with ceramics there is a progressive abandonment of shellmound construction in favor of flat cold shallow sites. Here we consider if these changes were reflected in the postmarital residence practice of coastal groups, i.e., if the arrival or intensification of contact with groups from the interior resulted in changes in this aspect of social structure among the coastal groups. To test the postmarital residence practice we analyzed within-group variability ratios between males and females, following previous studies on the topic. and between-group, correlations between Mahalanobis distances and geographic distances. The results suggest that in the pre-ceramic series a matrilocal, postmarital residential system predominated, while in the ceramic period there was a shift toward patrilocality. This favors the hypothesis that the changes experienced by coastal groups after 1200 B.P. affected not only their economy and material culture, but important aspects of their sociopolitical organization as well.