Spinocerebellar ataxia type 8 (SCA8) is a progressive neurological disorder caused by the expanded repeat CTA/CTG of two overlapping genes, ATXN8OS and ATXN8, expressed bidirectionally. Normal alleles have 15-50 repeats, and pathogenic alleles range from 71 to 1300 repeats. The disorder is relatively rare, accounting for about 2%-5% of the autosomal dominant forms of hereditary ataxia worldwide. However, the prevalence of disease-causing ATXN8OS/ATXN8 expansions is higher than the disease because of the reduced penetrance of the expanded allele. The aim of this study was to describe the first fully penetrant SCA8 family showing mixed Brazilian African and Amerindian origin. Eight members of this family were evaluated-the mother and seven offspring-through a complete neurological examination conducted at the Neurogenetics Clinic, HCFMRP-USP in Brazil. The number of CTA/CTG repeats was obtained after polymerase chain reaction (PCR) and fragment analysis. The haplotype analysis was conducted using a microsatellite marker, D13S1296, and four single nucleotide polymorphisms (SNPs), rs1831189, rs8002227, rs11841483, and rs72284461, all spanning a 70.1 Mb region on chromosome 13q21.3. The molecular analysis showed that the expansions ranged from 104 to 109 CTA/CTG repeats in the six affected individuals and were absent in two asymptomatic daughters (aged 53 and 40 years). Three SNPs cosegregate with the expanded alleles, confirming the connection between expansion and disease in this family. As the SCA8 diagnosis demands careful interpretation, we suggest the use of linkage analysis to observe segregation of the mutation, making more accurate its genotyping.

This study applies the Boundary Element Method (BEM) for the fracture failure modelling of three-dimensional concrete structures subjected to concentrated boundary conditions. The non-requirement of domain mesh by the BEM enables high accuracy in the domain fields assessment in addition to less complex remeshing procedures during crack propagation. However, concentrated boundary conditions often occur in fracture mechanics. The Lagrangian version of the BEM enforces such boundary conditions approximately by small length elements, which lead to numerical instabilities or even inaccurate problem representation. This study proposes a formulation for representing properly concentrated boundary conditions within the Lagrangian BEM framework. Nonlinear fracture mechanics describes the material failure processes herein. The classical cohesive crack approach governs the nonlinear energy dissipation processes, in which constant and tangent operators solve the resulting nonlinear system. Three applications demonstrate the accuracy of the proposed formulation, in which the BEM responses are compared against numerical and experimental results available in the literature.