A Large-Scale Full GBA1 Gene Screening in Parkinson's Disease in the Netherlands.

BACKGROUND: The most common genetic risk factor for Parkinson's disease known is a damaging variant in the GBA1 gene. The entire GBA1 gene has rarely been studied in a large cohort from a single population. The objective of this study was to assess the entire GBA1 gene in Parkinson's disease from a single large population. METHODS: The GBA1 gene was assessed in 3402 Dutch Parkinson's disease patients using next-generation sequencing. Frequencies were compared with Dutch controls (n = 655). Family history of Parkinson's disease was compared in carriers and noncarriers. RESULTS: Fifteen percent of patients had a GBA1 nonsynonymous variant (including missense, frameshift, and recombinant alleles), compared with 6.4% of controls (OR, 2.6; P < 0.001). Eighteen novel variants were detected. Variants previously associated with Gaucher's disease were identified in 5.0% of patients compared with 1.5% of controls (OR, 3.4; P < 0.001). The rarely reported complex allele p.D140H + p.E326K appears to likely be a Dutch founder variant, found in 2.4% of patients and 0.9% of controls (OR, 2.7; P = 0.012). The number of first-degree relatives (excluding children) with Parkinson's disease was higher in p.D140H + p.E326K carriers (5.6%, 21 of 376) compared with p.E326K carriers (2.9%, 29 of 1014); OR, 2.0; P = 0.022, suggestive of a dose effect for different GBA1 variants. CONCLUSIONS: Dutch Parkinson's disease patients display one of the largest frequencies of GBA1 variants reported so far, consisting in large part of the mild p.E326K variant and the more severe Dutch p.D140H + p.E326K founder allele. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.

Reliability and validity of the range of motion scale (ROMS) in patients with abnormal postures.

OBJECTIVE: Sustained abnormal postures (i.e., fixed dystonia) are the most frequently reported motor abnormalities in complex regional pain syndrome (CRPS), but these symptoms may also develop after peripheral trauma without CRPS. Currently, there is no valid and reliable measurement instrument available to measure the severity and distribution of these postures. The range of motion scale (ROMS) was therefore developed to assess the severity based on the possible active range of motion of all joints (arms, legs, trunk, and neck), and the present study evaluates its reliability and validity. METHODS: Inter- and intra-rater reliability of the ROMS was determined in 16 patients with abnormal sustained postures, who were videotaped following a standard video protocol in a university hospital. The recordings were rated by a panel of international experts. In addition, 30 patients were clinically tested with both the Burke-Fahn-Marsden (BFM) scale as well as the ROMS to assess construct validity. RESULTS: Inter-rater reliability for total ROMS scores showed an intra-class correlation coefficient (ICC) of 0.85. The majority of the scores for the separate joints (13 out of 18) demonstrated an almost perfect agreement with ICCs ranging from 0.81 to 0.94; of the other items, one showed fair, one moderate, and three substantial agreement. The ICCs for the intra-rater reliability ranged from moderate to almost perfect (0.68-0.98). Spearman's correlation coefficients between corresponding body areas as measured with the ROMS or BFM were all above 0.82. CONCLUSION: The ROMS is a reliable and valid instrument to evaluate the severity and distribution of sustained abnormal postures.