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1. This manuscript describes two different strategies to progress from the clinical assessment of patients to the identification of disease-causing mutations. In the first disease, recognition of a metabolic abnormality allowed direct molecular analysis of the causal gene.

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The life of William Osler, MD, spanned three nations and two continents and left an enduring and universal impact on medicine. Osler held professorships during his career in Montreal, Philadelphia, Baltimore, and Oxford. His achievements great and small during these periods have been medallically commemorated both in his lifetime and posthumuously.

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