Several epidemiological studies support low cancer rates in patients with neurodegenerative disorders, including Parkinson's disease, Huntington's disease, and Alzheimer's disease. Different ...mechanisms were raised as possible causes, from mutated tumor suppressor genes (PARKIN, PINK1) to small interfering RNA based on the CAG trinucleotide repeat expansions located in introns or untranslated regions. However, as every rule has an exception, some tumors have an increased incidence in these neurodegenerative diseases such as breast and skin cancer (melanoma). This mini-review aims to establish the epidemiology between these neurodegenerative disorders and cancer to determine the possible mechanisms involved and therefore set eventual therapeutic applications. According to our findings, we conclude the presence of an inverse relationship among most cancers and the aforementioned neurodegenerative disorders. However, this concept needs to be considered cautiously considering specific genetic and extra-genetic linkage factors for particular tumors.
More than 1,000 mutations mapping to 60 different loci have been recognized as the cause of hereditary ataxias. However, almost 50% of the cases are still genetically uncharacterized, with etiology ...remaining to be identified.1 Diagnosis and research in rare diseases such as ataxia has been significantly improved with the recent availability of next-generation sequencing technologies.2 In order to expand the phenotype recently described in ataxia due to STUB1 mutations and to illustrate the utility of clinical genomics in the diagnosis of ataxias, we present a 23-year-old patient who had ataxia plus myoclonus in whom exome sequencing revealed novel compound heterozygous mutations in the STUB1 gene.
Abstract Yerba mate tea is a very common beverage in some countries of South America. We conducted a case–control study on an individual basis using hospital records to investigate the association ...between Parkinson's disease (PD) and yerba mate intake. A case was defined as an age of ≥ 40 years with ≥ 1 year of PD. Each case was individually matched by two controls. Exposure was measured by yerba mate consumption, coffee, tea, and alcohol intake and smoking status. The sample consisted of 223 PD patients (mean age 68 years and mean disease duration 7.3 years) and 406 controls. There was an inverse association between yerba mate “ bombilla ” consumption and PD (OR 0.64, 95% CI: 0.54–0.76, p = 0.00001). A multivariate analysis with a logistic regression adjusted by sex, alcohol intake and smoking provided the following results: yerba mate (OR 0.63, 95% CI: 0.53–0.76), tea (OR 0.60, 95% CI: 0.42–0.86), coffee (OR 0.51, 95% CI: 0.35–0.73). We found an inverse association between yerba mate consumption and PD. These results led us to hypothesize that yerba mate may have a potential protective role in the development of PD.
Juvenile Huntington disease in Argentina Gatto, Emilia Mabel; Parisi, Virginia; Etcheverry, José Luis ...
Arquivos de neuro-psiquiatria,
01/2016, Letnik:
74, Številka:
1
Journal Article
Recenzirano
Odprti dostop
We analyzed demographic, clinical and genetic characteristics of juvenile Huntington disease (JHD) and it frequency in an Argentinean cohort. Age at onset was defined as the age at which behavioral, ...cognitive, psychiatric or motor abnormalities suggestive of JHD were first reported. Clinical and genetic data were similar to other international series, however, in this context we identified the highest JHD frequency reported so far (19.72%; 14/71). Age at onset of JHD is challenging and still under discussion. Our findings reinforce the hypothesis that clinical manifestations, other than the typical movement disorder, may anticipate age at onset of even many years. Analyses of JHD cohorts are required to explore it frequency in populations with different backgrounds to avoid an underestimation of this rare phenotype. Moreover, data from selected populations may open new pathways in therapeutic approaches and may explain new potential correlations between HD presentations and environmental or biological factors.
► The overall prevalence of LRRK2 G2019S mutation in this series was 5.45%. ► No R1441G substitution was identified in this series. ► PD in LRRK2 mutations carriers was indistinguishable for the ...idiopathic PD. ► Systemic imnuno-mediated disorders were identified in 2 of 3 G2019S carriers.
To determine clinical characteristics and frequency of leucine-rich repeat kinase 2 gene (LRRK2) mutations in a cohort of patients with Parkinson's disease (PD) from Argentina.
Variation in the LRRK2 gene represents the most common genetic determinant of PD, only few data are available from Latin-America.
Informed consent was obtained and all studies were approved by the Institutional Review Boards. Fifty five consecutive PD patients were recruited. A structured interview and neurological examination were used to collect demographic and clinical information. Blood samples were obtained and DNA extracted from patient venous blood. All LRRK2 exons from 25 exon to 51 exon were screened in all patients.
Clinical and molecular data of 55 patients with PD were analyzed. Mean age was 68.8±10.6 years. Jewish and Basque ancestries were found positive in 9 and 7 patients, respectively; family history of PD was identified in 16 patients. The G2019S mutation was present in 3 Ashkenazi Jewish subjects (5.45%); all of them reported family history of PD in first-degree relatives. Although Argentina possesses one of the most important Basque communities outside Spain, non R1414G mutation was identified in this cohort. Eleven single polymorphisms (SNP) were identified in this cohort. The mean age at onset was higher in G2019S mutation carriers than non-carriers (66.67 vs 58.78 years). Asymmetrical tremor as initial symptom and non-motor symptoms occurred at similar frequencies in both groups. The G2019S mutation carriers showed a non significant increase in dyskinesias, and 2/3 developed Dopamine Dysregulation Syndrome and visual hallucinations. Systemic disorder identified in G2019S mutation carriers included: celiac disease, hypothyroidism, Hashimoto's Thyroiditis and arterial hypertension.
The prevalence of LRRK2 G2019S mutation in this Argentinean cohort was similar to other international series, with a higher prevalence in Ashkenazi Jewish. The phenotype was indistinguishable from patients with idiopathic PD. Interestingly, we identified immune mediated disorders in two PD patients carrying the G2019S mutation. Within this context, recent studies have identified full-length LRRK2 as a relatively common constituent of many cell types in the immune system including human peripheral blood mononuclear cells. Nevertheless, a casual association could not be excluded and the analysis of more extensive series is required.
BackgroundHolmes tremor is a rare symptomatic movement disorder, characterized by a combination of resting, postural, and intention tremor. It is usually caused by lesions in the brainstem, thalamus, ...and cerebellum. Despite pharmacological advances, its treatment remains a challenge; many medications have been used with various degrees of effectiveness. Stereotactic thalamotomy and deep brain stimulation in the ventralis intermedius nucleus have been effective surgical procedures in cases refractory to medical treatment. Case ReportHere we report a young woman with topiramate-responsive Holmes tremor secondary to a brainstem cavernoma. DiscussionHerein we report a Holmes tremor responsive to Topiramate.
BACKGROUNDDystonic postures possess a great number of differential diagnoses. PHENOMENOLOGY SHOWNWe describe a pseudodystonic posture in a 61-year-old woman with skeletal and extra-skeletal ...abnormalities. EDUCATIONAL VALUEKlippel-Feil syndrome represents an unusual cause of pseudodystonic posture to be considered in the differential diagnosis of dystonia.
Abstract Background and purpose The number of restless legs syndrome (RLS) prevalence studies performed outside Europe and North America remains small. We conducted a community-based study to ...estimate the relative prevalence of RLS in Argentina. Patients and methods A total sample of 471 participants from high (Buenos Aires) and low population density areas (three cities with <35,000 inhabitants), completed a self-assessment questionnaire, including the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria, to determine RLS symptoms. Results In the present study, the four RLS criteria were reported in 20.2%. In accordance with other studies, we found a female/male ratio of 3:1, with women being younger than men. However, RLS prevalence in “clinically significant” participants, that is symptoms present at least two or more times a week, were 10.8% (12.4% in participants from high population density versus 2.60% in participants from low population density areas). Conclusions In the present study, RLS appears as a common disorder in this population. The RLS prevalence found is in agreement with some epidemiological reports from the American and European populations but it is significantly higher than the prevalence reported for Native South Americans (i.e., 0.8–3.2%). These differences could be explained by the composition of the Argentinean population with predominantly European roots. Taking into account the significant impact of RLS on health and quality of life, our study represents a preliminary approach to characterize this chronic disease in this community.
There have been no specific guidelines regarding which genes should be tested in the clinical setting for Parkinson's disease (PD) or parkinsonism. We evaluated the types of clinical genetic testing ...offered for PD as the first step of our gene curation.
The National Institutes of Health (NIH) Genetic Testing Registry (GTR) was queried on 12/7/2020 to identify current commercial PD genetic test offerings by clinical laboratories, internationally.
We identified 502 unique clinical genetic tests for PD, from 28 Clinical Laboratory Improvement Amendments (CLIA)-approved clinical laboratories. These included 11 diagnostic PD panels. The panels were notable for their differences in size, ranging from 5 to 62 genes. Five genes for variant query were included in all panels (SNCA, PRKN, PINK-1, PARK7 (DJ1), and LRRK2). Notably, the addition of the VPS35 and GBA genes was variable. Panel size differences stemmed from inclusion of genes linked to atypical parkinsonism and dystonia disorders, and genes in which the link to PD causation is controversial.
There is an urgent need for expert opinion regarding which genes should be included in a commercial laboratory multi-gene panel for PD.
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