Mutations in the gene leucine-rich repeat kinase 2 (LRRK2) have been recently identified in families with Parkinson's disease (PD). However, the prevalence and nature of LRRK2 mutations, the polymorphism content of the gene, and the associated phenotypes remain poorly understood. We performed a comprehensive study of this gene in a large sample of families with Parkinson's disease compatible with autosomal dominant inheritance (ADPD). The full-length open reading frame and splice sites of the LRRK2 gene (51 exons) were studied by genomic sequencing in 60 probands with ADPD (83% Italian). Pathogenic mutations were identified in six probands (10%): the heterozygous p.G2019S mutation in four (6.6%), and the heterozygous p.R1441C mutation in two (3.4%) probands. A further proband carried the heterozygous p.I1371 V mutation, for which a pathogenic role could not be established with certainty. In total, 13 novel disease-unrelated variants and three intronic changes of uncertain significance were also characterized. The phenotype associated with LRRK2 pathogenic mutations is the one of typical PD, but with a broad range of onset ages (mean 55.2, range 38–68 years) and, in some cases, slow disease progression. On the basis of the comprehensive study in a large sample, we conclude that pathogenic LRRK2 mutations are frequent in ADPD, and they cluster in the C-terminal half of the encoded protein. These data have implications both for understanding the molecular mechanisms of PD, and for directing the genetic screening in clinical practice.

Quality of life in multiple sclerosis has been often measured through the SF-36 questionnaire. In this study, validation of the SF-36 summary scores, its 'physical' component, and its 'mental' component was attempted by exploring the joint predictive power of disability (EDSS score), of anxiety and depression (HADS-A and -D scores, respectively), and of disease duration, progression type, age, gender and marital status. The sample consisted of 75 patients suffering from multiple sclerosis admitted to an inpatient rehabilitation unit. The interplay between potential predictors was assessed through a particular regression model (classification and regression tree, CART). Two main advantages of this technique are its robustness with respect to distributional assumptions (rarely met by scores coming in from questionnaires) and its sensitivity to high-order interactions, between independent variables, difficult to detect through conventional multiple regression. Predictive variables for physical component of the SF-36 were EDSS and HADS-D (36.8% variance explanation). The only predictive variable for mental component of SF-36 was HADS-D (39.1% variance explanation). Results confirm previous findings showing that in patients with multiple sclerosis quality of life is heavily determined by person's mood, whatever his/her neurological or functional severity. The usefulness and validity of the SF-36 as an index representative of quality of life is debatable, as long as depression explains much of its variance. Further refinement of quality of life definition and measurement is worth further psychometric and statistical research.