Tom Youngs will miss England's summer tour to New Zealand for family reasons.
The Leicester hooker - who made his international debut against Fiji during the autumn of 2012 - will remain at home to support his ill wife, a decision national coach Stuart Lancaster has fully endorsed.
"Our thoughts are with Tom and Tiffany at this time and it is entirely right that he stays at home to support her and their daughter Maisie," "Everyone in the England squad sends them our best wishes."
Youngs' British and Irish Lions team-mates Alex Corbisiero and Tom Croft will also not be in the squad for the trip.
Northampton prop Corbisiero and Leicester flanker Croft are both ready to return from long-term injuries, but the England coaching staff are not willing to take any risks with the 2015 World Cup in mind.
Lancaster is also unable to select wings Christian Wade and Jack Nowell due to respective foot and knee problems. Now there are also doubts over the fitness of Gloucester centre Billy Twelvetrees and Bath hooker Rob Webber after both players were hurt in action for their club sides recently.
Twelvetrees suffered ankle trouble in Gloucester's 38-30 Aviva Premiership victory over London Irish on Saturday.
Webber, meanwhile, suffered a knee injury in Bath's 19-19 draw with Northampton on Friday night and is now facing a race against time to be ready for the trip.
"Alex and Tom have worked really hard to come back before the end of the season but they will not have played enough rugby for them to be considered for such a tour. It's the same with Christian Wade," Lancaster said on the RFU's official website.
"They have all had significant injuries and their return to play has been carefully managed in conjunction with their clubs. It will be a short-term loss but a long-term gain for us and their clubs as we enter a huge 18 months."
Lancaster will delay finalising his New Zealand tour party as long as possible to combat club and country fixture congestion.
The England boss will wait on the outcome of a host of club play-offs and finals before selecting a 40-plus group for the three-Test series against the reigning world champions.
None of the Aviva Premiership finalists will be able to part in the first Test in Auckland on June 7, as it falls just seven days after the domestic showpiece at Twickenham.
European competitions could also cause a further selection headache for Lancaster; Bath take on Northampton in the Amlin Challenge Cup final on May 23, then Saracens face Toulon in the Heineken Cup final the following day.
Now it has also been confirmed that Wasps will face Stade Francais in the seventh-place play-off to qualify for the new European Champions Cup, with the second leg scheduled for on May 24 in Paris.
England entertain the Barbarians at Twickenham on June 1 before heading to New Zealand, where they will face the All Blacks in Test matches staged in Auckland, Dunedin and Hamilton.