The four crew members are presumed dead pending positive identification, The San Diego Union-Tribune quoted Marine spokeswoman Capt. Morgan Frazer as saying.
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The nearby Naval Air Facility El Centro messaged that the crash site was north of Plaster City, west of El Centro. The names of the crewmembers will be withheld until 24 hours after their relatives are notified, the Miramar base said.
In total, 13 USA service members have been killed in separate aircraft crashes since March 14: Two Navy aviators died when their F/A-18F Super Hornet crashed off Florida, and seven airmen were killed on March 15 when their Air Force HH-60 crashed in western Iraq, near the Syrian border.
Marine officials said it was too early to determine what caused Tuesday's crash.
"We ask that you continue to be patient with us as the situation unfolds".
Tuesday's California crash is the deadliest involving a Marine aircraft since a KC130T transport plane went down in MS last July, killing 15 Marines and a sailor.
On April 4, 2017 at the same base, a Super Stallion from the Miramar-based "Flying Tigers" of Marine Heavy Helicopter Squadron 361 did a "CFIT" - controlled flight into terrain - while performing defensive maneuvers. It is essentially used for minesweeping, transportation and is capable of carrying dozens of troops and tons of cargo.
A CH-53E Super Stallion helicopter takes off on July 30, 2013. The Marines ultimately ruled that crash was the result of pilot error, leading two of the massive aircraft to collide in the air. In addition, U.S.A officials have not confirmed whether those killed were Marines.
"No other injuries were reported to personnel on the ground nor damage to infrastructure at the airport", the statement added.