Thought to have been designed by local architect Michael Priestley, it was built in 1740 for Andrew Knox, M.P. for Donegal, after he married Prehen heiress Honoria Tomkins two years earlier. Andrew Knox's family owned the house for 170 years. After being seized by the government after the 1914–18 war, Prehen House was brought back into another branch of the Knox family.
The Department of the Environment has listed Prehen as a grade A building of national importance.
Prehen House is home to one of Ireland's greatest love stories, the legend of Half Hung MacNaghten.
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