Novel mutations in the sacsin gene in ataxia patients from Maritime Canada.

We ascertained two families in Eastern Canada segregating a form of ataxia consistent with a recessive mode of inheritance. We performed a whole genome scan using dense SNP genotyping, and despite an absence of shared homozygosity in the families we defined linkage to a small region on chromosome 13. Direct DNA resequencing was employed to screen biologically relevant candidate genes in the interval, and two presumptive pathogenic mutations were found in the gene encoding sacsin. One variant is an obligate truncating mutation, the second is a missense variant in a highly conserved residue. Unexpectedly, one family was homozygous for the missense mutation, the other compound heterozygous for the two mutations. Our results expand the genotype phenotype correlation of mutations in the sacsin gene, and highlight the challenge of diagnosing genetically heterogeneous disorders on primarily clinical grounds. We demonstrate that whole genome genotyping on a modest scale can be productive in research, and potentially in a clinical context.

Commissioning, clinical implementation and quality assurance of Siemen's Virtual Wedge.

This report presents the results of commissioning, clinical implementation and quality assurance of Siemens Virtual Wedge. Our measurements show that: (1) wedge factors are within 2% of unity, (2) percentage depth doses are within 1% of open beam data, and (3) wedged beam profiles can be modeled similarly to a physical wedge and follow a well defined equation to facilitate modeling of an arbitrary wedge angle. The gantry angle dependence of wedge profiles is similar to open beam profiles. The output of wedged fields is linear with delivered monitor units within 1%. Quality assurance results indicate the wedge profiles are very stable over time. Day to day variations of two points measured along the wedge gradient direction are within 1.5%.