The genetics of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD)

Published on July 1, 2014   35 min

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My name is Rohan de Silva, and I'm from the UCL Institute of Neurology at University College London. And today, my lecture will focus on the genetics of two sporadic Parkinsonian disorders-- Progressive Supranuclear Palsy and Corticobasal Degeneration, also known by the acronyms PSP and CBD.
Although these disorders are very rare, they are primary tauopathies. That is, they are caused by tau protein dysfunction. And I will come back to this later. And they're therefore good models for the study of the central role of the tau protein in neurodegeneration. And although they are sporadic disorders without any inherited gene defects, it is clear from genetic association that common polymorphism in the tau gene is a significant risk factor for PSP and CBD. As a result, PSP in particular has been a good example for illustrating the possible functional basis of such genetic associations, and these go beyond the missense changes that affect the coding sequences of genes. More recently, additional genetic factors were identified in a genome-wide association study that implicates cellular processes other than tau. And I will describe these in the last part of this lecture.
From a genetic point of view, we have the inherited Mendelian disorders that are relatively rare. But in most cases, a coding mutation is inherited from parents to offspring in an autosomal dominant or recessive fashion. These Mendelian mutations confer higher risk. They're depending on penetrance, or the severity of the coding change, due to the inherited mutation or due to interaction with other genes. The carrier of the mutated gene is more or less certain of inheriting the disorder.

The genetics of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD)

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