Buccal Cell Micronucleus Frequency Is Significantly Elevated in Patients with Spinocerebellar Ataxia Type 2.

Spinocerebellar ataxia type 2 (SCA2) is part of a group of at least nine dominantly inherited disorders characterized by progressive degeneration of specific neuronal populations and a shared mutational mechanism involving the expansion of a CAG repeat tract in coding regions of novel genes. Efforts have been made to identify biomarkers of disease progression, which would allow timely preventive therapeutic interventions. In the present study was assessed the influence of several genome instability biomarkers on SCA2 clinical severity. A case-control design was applied on exfoliated epithelial buccal cells to determine micronuclei frequency and others nuclear anomalies, using 5% Giemsa stains. The slides were analyzed under 1000X magnification and nuclei morphological anomalies were identified according to Tolbert PE, et al. (1992) and Bolognesi C, et al. (2013) criteria. It was found a highly significant increase in micronuclei frequency in cases related to age and sex-matched healthy controls (p <0.001). There was a trend for karyolytic, pyknotic and condensed chromatin cells to be increased in SCA2 cases, and a significant association was found between binucleated cells and disease duration (r = 0.46; p = 0.027). Nor the CAG repeat length neither the age at onset correlated significantly with any of the studied markers (p >0.05). Our results are consistent with report previous in similar neurodegenerative diseases, and suggest that micronuclei and binucleated cells constitute potential peripheral biomarkers for SCA2. These results should be validated by other studies.

Association of glutathione S-transferase omega polymorphism and spinocerebellar ataxia type 2.

BACKGROUND: Spinocerebellar ataxia type 2 is a neurodegenerative disorder caused by a CAG repeat expansion in ATXN2 gene. There is high clinical variability among affected patients suggesting the occurring of modifier genes influencing the clinical phenotype. OBJECTIVE: The objective is to assess the association of GSTO1 rs4925 and GSTO2 rs2297235 SNPs on the clinical phenotype in SCA2 patients. METHODS: A case-control study was performed in a sample of 120 SCA2 Cuban patients and 100 healthy subjects. Age at onset, 60° Maximal Saccade Velocity and SARA score were used as clinical markers. GSTO1 rs4925 and GSTO2 rs2297235 SNPs were determined by PCR/RFLP. RESULTS: Distribution of the GSTO1 alleles and genotypes was nearly equal between the control group and SCA2 patients. GSTO1 genotypes were not associated to clinical markers in SCA2 patients. Distribution of the GSTO2 "G" allele and "AG" genotype differed significantly between SCA2 patients and controls. Symptomatic SCA2 individuals had a 2.29-fold higher chance of carrying at least one "G" allele at GSTO2 rs2297235 than controls (OR=2.29, 95% CI: 1.29-4.04). GSTO2 genotypes were significantly associated to age at onset (p=0.037) but not to 60° Maximal Saccade Velocity or SARA score in SCA2 patients. CONCLUSION: The GSTO1 rs4925 polymorphism is not associated to SCA2. Meanwhile, the GSTO2 rs2297235 "AG" genotype is associated to SCA2 but failed to show any association with clinical markers, with the exception of a potential association with the age at disease onset.

Genetic features of Huntington disease in Cuban population: implications for phenotype, epidemiology and predictive testing.

Huntington disease is the most frequent polyglutamine disorder with variable worldwide prevalence. Although some Latin American populations have been studied, HD prevalence in Cuban population remains unknown. In order to characterize the disease in Cuba, the relative frequency of HD was determined by studying 130 patients with chorea and 63 unrelated healthy controls, emphasizing in the molecular epidemiology of the disease. Sixty-two patients with chorea belonging to 16 unrelated families carried a pathological CAG expansion in the HTT gene, ranging from 39 to 67 repeats. Eighty-three percent of them come from the eastern region of the country. A significant inverse correlation between age at onset and expanded CAG repeats was seen. Intermediate alleles in affected individuals and controls represented 4.8% and 3.97% respectively, which have been a putative source of de novo mutation. This study represents the largest molecular characterization of Huntington disease in the Cuban population. These results may have significant implications for an understanding of the disease, its diagnosis and prognosis in Cuban patients, giving health professionals the tools to implement confirmatory genetic testing, pre-symptomatic testing and clinical trials in this population.