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Background: Schizophrenia (SCZ) is a very heterogeneous disease that affects approximately 1% of the general population. Recently, the genetic complexity thought to underlie this condition was further supported by three independent studies that identified an increased number of damaging de novo mutations DNM in different SCZ probands. While these three reports support the implication of DNM in the pathogenesis of SCZ, the absence of overlap in the genes identified suggests that the number of genes involved in SCZ is likely to be very large; a notion that has been supported by the moderate success of Genome-Wide Association Studies (GWAS)., Methods: To further examine the genetic heterogeneity of this disease, we resequenced 62 genes that were found to have a DNM in SCZ patients, and 40 genes that encode for proteins known to interact with the products of the genes with DNM, in a cohort of 235 SCZ cases and 233 controls., Results: We found an enrichment of private nonsense mutations amongst schizophrenia patients. Using a kernel association method, we were able to assess for association for different sets. Although our power of detection was limited, we observed an increased mutation burden in the genes that have DNM.

Importance: Autosomal recessive cerebellar ataxia type I, also known as recessive ataxia of Beauce, is a slowly progressive ataxia that leads to moderate disability with gait ataxia, dysarthria, dysmetria, mild oculomotor abnormalities, and diffuse cerebellar atrophy on brain imaging. Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene, located on chromosome 6p25, were first reported in patients who originated from a region known as "Beauce" in the province of Quebec, Canada., Objective: To better evaluate the prevalence of SYNE1 mutations in individuals with mild pure cerebellar ataxia and cerebellar atrophy, we screened the gene in additional French-Canadian (FC) families and individuals from other populations., Design, Setting, and Participants: Study participants were referred by their treating physician on the basis of core features of autosomal recessive cerebellar ataxia type I. After excluding individuals with known SYNE1 mutations, our cohort was composed mainly of 19 FCs and 21 individuals from other ethnic backgrounds., Interventions: Extraction of DNA from blood samples and complete resequencing of the SYNE1 gene., Main Outcomes and Measures: The involvement of SYNE1 mutations in individuals with ataxia worldwide by resequencing the SYNE1 gene., Results: Two novel truncating mutations were found among the FC participants, and 2 other novel mutations were found in a patient from France and a patient from Brazil (1 mutation each)., Conclusions and Relevance: This is the second report, to our knowledge, of SYNE1 gene mutations in a population other than FCs. These data suggest that mutations in SYNE1 should be investigated in families with cerebellar ataxia who live outside the FC region.

Essential tremor (ET) is a complex genetic disorder for which no causative gene has been found. Recently, a genome-wide association study reported that two variants in the LINGO1 locus were associated to this disease. The aim of the present study was to test if this specific association could be replicated using a French-Canadian cohort of 259 ET patients and 479 ethnically matched controls. Our genotyping results lead us to conclude that no association exists between the key variant rs9652490 and ET (P(corr) = 1.00).