We have several TLs with surviving Miguel da Paz. I wonder what would happen if only child of Manuel of Portugal and Isabella of Castile is born as girl (propably also named Isabella)?

First scenario (that one is easy): both daughter and mother survives, but Isabella and Manuel have no more children. In such case younger Isabella, undisputed heiress to all 3 Kingdoms, could just marry her cousin Jaime Braganza (who is next in succession line to the Portuguese throne after her, or Teodosio, if Jaime's OTL marriage is not butterflied away) and we'll have Braganza Iberian Union.

Second scenario (that one is more complicated): Say Isabella of Castile still dies soon after giving birth, but her daughter is healthly and lives to adulthood. Manuel as 30 years old widower without sons would surely remarry, and if he had son(s), he'll be heir to Portuguese throne. What would happen then with Manuel's oldest daughter? She can't marry future Portuguese King, who'll be her half-brother ITTL. Braganza OTOH is still possible.
 
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Maybe she marries one of her Austrian or, given the POD, English cousins? Say some of Juana and Philip's daughters are born as sons, so instead of OTL's Eleanor, Charles, & Isabella of Austria we have Philip (1498), Charles (1500), and Maximilian (1501).

Here Isabella II likely marries either Charles or Maximilian (depending on if Philip Jr. inherits Austria and Burgundy or if one of them gets given to Charles). While I know people will want to prevent the inbreeding palooza in Spain, Habsburg like incest seems like the only acceptable alternative to the Iberian shuffle between Castile, Aragon, and Portugal.
 
Marriage of Isabella to Manuel was intended to prevent Philip Habsburg from inheriting Castile, so marrying her heiress to Habsburg makes little sense.
 
A wedding for young Isabella is really complicated: no way any of Juana's children, a son from a second wedding of Ferdinand of Aragon would be too young for her like a child of either Maria or Catalina so our only options are: Braganza, a prince of Aragon from the branch of Naples or really unlikely but still not impossible the King of Navarre or Henry of England, Duke of York or a prince of Savoy
 
It all depends on which scenario happens. If it's the first, where Isabella's mother is alive, then a Habsburg match is more likely. Her mother would be the queen of Castile, while Ferdinand wouldn't, and he would have less influence on the decisions regarding his granddaughter. Manuel would do everything possible to achieve within Castile the same influence that Ferdinand achieved with Isabela I. As it was Ferdinand who personally disliked Philip of Habsburg, I could see the new royal couple (Manuel and Isabella) actually pushing for a match with one of Philip's sons exactly in order to show that they are the ones who have power in Castile, and not Ferdinand anymore.

If it's the second scenario that happens, than the situation is much more complicated. First, the succession must be settled. Manuel's daughter should be the queen, but Juana could actually states that her claim is better by proximity of blood, and Philip could support it. With Miguel da Paz being male there was no discussion about it, but here the two options are an infant girl and a woman married to a foreigner. Both Ferdinand and Manuel would support "Isabella the Younger", but there would be a dispute between them about who would have more rigths over her regency: her father or her grandfather. Also, considering that Manuel would have a living daughter from his first wife, would it be allowed to him to marry the aunt of his daughter? I can't remember any case such situation happened IOTL, only cases that a remarriage to a sibling was allowed but then the first marriage was childless.
 
It all depends on which scenario happens. If it's the first, where Isabella's mother is alive, then a Habsburg match is more likely. Her mother would be the queen of Castile, while Ferdinand wouldn't, and he would have less influence on the decisions regarding his granddaughter. Manuel would do everything possible to achieve within Castile the same influence that Ferdinand achieved with Isabela I. As it was Ferdinand who personally disliked Philip of Habsburg, I could see the new royal couple (Manuel and Isabella) actually pushing for a match with one of Philip's sons exactly in order to show that they are the ones who have power in Castile, and not Ferdinand anymore.

If it's the second scenario that happens, than the situation is much more complicated. First, the succession must be settled. Manuel's daughter should be the queen, but Juana could actually states that her claim is better by proximity of blood, and Philip could support it. With Miguel da Paz being male there was no discussion about it, but here the two options are an infant girl and a woman married to a foreigner. Both Ferdinand and Manuel would support "Isabella the Younger", but there would be a dispute between them about who would have more rigths over her regency: her father or her grandfather. Also, considering that Manuel would have a living daughter from his first wife, would it be allowed to him to marry the aunt of his daughter? I can't remember any case such situation happened IOTL, only cases that a remarriage to a sibling was allowed but then the first marriage was childless.
Anything is permitted,even if you marry your own siblings,as long as you have the stamp of papal approval,which isn’t actually that hard to get in the 16th century.
 
Anything is permitted,even if you marry your own siblings,as long as you have the stamp of papal approval,which isn’t actually that hard to get in the 16th century.
Well, hats off to these guys, they outranked the Habsburgs!

But, in the other hand, Manuel could try to appease the Habsburgs in order to have his support for the claims of his daughter and marry Philip's sister Margaret instead (and she wouldn't marry the Duke of Savoy ITTL), and, at the same time, promise Isabella II to a son of Philip and Joanna. This way, any future male heir of Manuel would be related to the Habsburgs, while Philip could secure to Castilian throne to a son by marriage.
 
Also, considering that Manuel would have a living daughter from his first wife, would it be allowed to him to marry the aunt of his daughter? I can't remember any case such situation happened IOTL, only cases that a remarriage to a sibling was allowed but then the first marriage was childless.
Sigismund III Vasa had children with his first wife, Anna of Austria, after her death he remarried her sister Constance, so I see no problem there.
 
I think the daughter could marry Ferdinand of Naples the OTL husband of Germaine.

Seconded. In a situation where Isabella of Aragon dies, if Manuel can't remarry to his OTL 2e wife, let him remarry to Fernando's niece, Giovanna of Naples. If little Isabel da Paz marries Ferrante after that, all the Trastamaras are getting is the reunified Castile-Aragon-Naples of OTL (assuming Fernando's second marriage still has the same outcome) just by different means.
 
Well, hats off to these guys, they outranked the Habsburgs!

The duke of Württemberg-Montbéliard managed in 1719 to marry his kids from his first morganatic wife to the kids of his mistress. He was father of both sets of kids (even though the "official" father of the mistress' were her husband).

To make rhings even more fun, both marriages (his son and daughter married the mistress' son and daughter) produced offspring, who left descent. And the duke ACTUALLY tried to petition the emperor to let his eldest son be styled Erbprinz von Mömpelgard/Prince Héréditaire de Montbéliard. Karl VI said not a chance, but the fights for them to succeed in Montbéliard/Coligny inheritance via the duke's mom went on until the 1760s.
 
Don't forget the fact that Henry VIII actually toyed with the idea of asking for dispensation to let Fitzroy marry Mary before the annulment of his marriage to her mother, which the Pope was actually willing to do.
 
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