When mutations in LRRK2 linked to Parkinson’s disease were first described back in 2004, an immediate question was whether there might be similar mutations in the paralogous protein LRRK1 – a protein that shares many of the features of LRRK2. Thus far, this does not seem to be the case, although it is not an issue that has been looked at in detail for a number of years. Eva Schulte and Juliane Winkelmann, neurologists based in Munich, have been looking at coding variations in LRRK1 and risk of developing Parkinson’s disease in a series of families that they have been seeing in clinic. We worked with them to look at some of the biological properties of these variants, expressing them in cells. Based upon these genetic and cellular studies, there is some evidence that rare variants in LRRK1 can increase risk for PD, but this study really highlights the difficulties in interpreting the role of rare coding changes in disease. For sure, this is an issue that needs a lot more research before we have a definitive conclusion.
Read more about this study in Eva’s article in Neurogenetics: