Francis and Margaret's children included Henry, whose daughter Frances briefly held Boxley; Francis, who was at King's College, Cambridge, in 1639; Edwin, an MP who successfully sued his niece to regain Boxley, but whose son died without issue; and Elizabeth, whose grandson Robert Marsham, 1st Baron Romney (1685–1724), eventually inherited Boxley.
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In 1622 he rallied the defense of Jamestown which was attacked by Native Americans, during which the lives of some 400 settlers were lost and he then oversaw the contraction of the colony from scattered outposts into a defensive core.
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Francis Wyatt's grandfather was Sir Thomas Wyatt the younger, who had led the Kent faction of Wyatt's rebellion to the Spanish marriage of Queen Mary in support of Lady Elizabeth.
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