While reading Rivers of Gold (see below) NewMexiKen checked out the genealogy in the appendices. This was the most remarkable find:
King Manuel of Portugal (b. 1469, d. 1521) first married Isabel of Aragon, daughter of Queen Isabel and King Fernando. She died in childbirth in 1498.
So then King Manuel married her 16-year-old sister, Maria of Aragon. She died in 1517.
He then married Leonor, the daughter of Juana, the oldest of Fernando and Isabel’s daughters (that is, his niece by two marriages).
He had children with all three. What a guy.