Autosomal dominant lateral temporal epilepsy (EPT; OMIM 600512) is a form of epilepsy characterized by partial seizures, usually preceded by auditory signs. The gene for this disorder has been mapped by linkage studies to chromosomal region 10q24. Here we show that mutations in the LGI1 gene segregate with EPT in two families affected by this disorder. Both mutations introduce premature stop codons and thus prevent the production of the full-length protein from the affected allele. By immunohistochemical studies, we demonstrate that the LGI1 protein, which contains several leucine-rich repeats, is expressed ubiquitously in the neuronal cell compartment of the brain. Moreover, we provide evidence for genetic heterogeneity within this disorder, since several other families with a phenotype consistent with this type of epilepsy lack mutations in the LGI1 gene.

Background: Parkinson's disease (PD) involves environmental risk and protective factors as well as genetic variance. Most of the research in genomics has been done in subjects of European ancestry leading to sampling bias and leaving Latin American populations underrepresented. Objective: We sought to phenotype and genotype Costa Rican PD cases and controls. Methods: We enrolled 118 PD patients with 97 unrelated controls. Collected information included demographics, exposure to risk and protective factors, motor and cognitive assessments. We sequenced coding and untranslated regions in familial PD and atypical parkinsonism-associated genes including GBA, SNCA, VPS35, LRRK2, GCH1, PRKN, PINK1, DJ-1, VPS13C, ATP13A2. Results: Mean age of PD probands was 62.12 ± 13.51 years, 57.6% were male. Prevalence of risk and protective factors reached 30%. Physical activity significantly correlated with better motor performance despite years of disease. Increased years of education were significantly associated with better cognitive function, whereas hallucinations, falls, mood disorders and coffee consumption correlated with worse cognitive performance. We did not identify an association between tested genes and PD or any damaging homozygous or compound heterozygous variants. Rare variants in LRRK2 were nominally associated with PD, six were located between amino acids p.1620-1623 in the C-terminal-of-ROC (COR) domain of LRRK2. Nonsynonymous GBA variants (p.T369M, p.N370S, p.L444P) were identified in three healthy individuals. One PD patient carried a pathogenic GCH1 variant, p.K224R. Conclusion: This is the first study that reports on sociodemographic, risk factors, clinical presentation and genetics of Costa Rican patients with PD.

IF and Fornaguera-Trías J ( ) Corrigendum: Clinical and genetic analysis of Costa Rican patients with Parkinson's disease.