Juana I of Castile is born male (Ferdinand/Alfonso anyone?) but has very similar personality traits, but isn't called mad.... This is one of several marriages I could see happening, also I imagine things would go better for Catherine of Aragon here, as her marital value won't deteriorate after her mother's death (The succession in Castile is clear here) Also, Isabella of Aragon doesn't die (nor does her first husband) , thanks to my own discretion and the fact that she isn't traveling halfway across Iberia to get the damn Cortes of Aragon to swear her in. Also, Maria of Aragon marries Phillip "The Fair" and while he's still a tool, she would probably be much calmer about her husband's infidelities.
King Ferdinand VI of Spain and Jure Uxois King of Naples (b.1479, d.1555) m. Giovanna of Naples, Queen of Spain and Suo Jure Queen of Naples in 1495 (b.1479, d.1549) (1) had issue
1) Juana of Aragon, Queen of Portugal (b.1497, d.1550) m. King João III of Portugal (b.1497, d.1553) had issue
2) Juan, Prince of Asturias, later Juan III of Spain (b.1499, d.1562) m. Eleanor of Austria, Queen of Spain (b.1500, d.1563) (2) had issue
3) Stillborn son (1501)
4) Alfonso III of Naples (b.1504, d.1560) m. Alessandra d'Este, Queen of Naples (3) (b.1505, d.1550) had issue second marriage to Isabel de Toledo, Queen of Naples in 1551 (b.1530, d.1602), had issue
5) Isabella of Aragon, Queen of England (b.1506, d.1567) m. King Henry IX of England (b.1506, d.1552) (4)
6) Infante Pedro, Duke of Cadiz (b.1509, d.1573) m. Buenaventura of Navarre, Duchess of Cadiz (b.1505, d.1554)
7) Blanca of Aragon, Nun/Abbess (b.1511, d.1580) (5)
(1) His cousin, Ferdinand never remarries, heartbroken after his beloved wife's death
(2) A daughter of Maximillian I and Bianca Maria Sforza
(3) Eldest child of Alfonso I d'Este and Lucrezia Borgia is born female and survives infancy
(4) Eldest son of Henry VIII and Catherine of Aragon, since they marry shortly after Henry's fourteenth birthday, he has an heir in the cradle before his father drops dead.
(5) His daughter becomes a nun, and even though Ferdinand isn't too keen on the idea, he decides it is better than making her marry someone she will resent. Blanca inherits her father's impressive longevity, dying of natural causes at the age of seventy-nine.
King Ferdinand VI of Spain and Jure Uxois King of Naples (b.1479, d.1555) m. Giovanna of Naples, Queen of Spain and Suo Jure Queen of Naples in 1495 (b.1479, d.1549) (1) had issue
1) Juana of Aragon, Queen of Portugal (b.1497, d.1550) m. King João III of Portugal (b.1497, d.1553) had issue
2) Juan, Prince of Asturias, later Juan III of Spain (b.1499, d.1562) m. Eleanor of Austria, Queen of Spain (b.1500, d.1563) (2) had issue
3) Stillborn son (1501)
4) Alfonso III of Naples (b.1504, d.1560) m. Alessandra d'Este, Queen of Naples (3) (b.1505, d.1550) had issue second marriage to Isabel de Toledo, Queen of Naples in 1551 (b.1530, d.1602), had issue
5) Isabella of Aragon, Queen of England (b.1506, d.1567) m. King Henry IX of England (b.1506, d.1552) (4)
6) Infante Pedro, Duke of Cadiz (b.1509, d.1573) m. Buenaventura of Navarre, Duchess of Cadiz (b.1505, d.1554)
7) Blanca of Aragon, Nun/Abbess (b.1511, d.1580) (5)
(1) His cousin, Ferdinand never remarries, heartbroken after his beloved wife's death
(2) A daughter of Maximillian I and Bianca Maria Sforza
(3) Eldest child of Alfonso I d'Este and Lucrezia Borgia is born female and survives infancy
(4) Eldest son of Henry VIII and Catherine of Aragon, since they marry shortly after Henry's fourteenth birthday, he has an heir in the cradle before his father drops dead.
(5) His daughter becomes a nun, and even though Ferdinand isn't too keen on the idea, he decides it is better than making her marry someone she will resent. Blanca inherits her father's impressive longevity, dying of natural causes at the age of seventy-nine.