Officers responded at 12:28 a.m. to a report of a major collision at Capitol Expressway and Snell Avenue, police said.
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After a preliminary investigation, officers determined a white 2012 Chevrolet Malibu being driven by a 25-year-old woman was traveling west on Capitol Expressway. For an unknown reason, the Chevy crossed into the opposite lanes of traffic, colliding head on into a silver 2004 Lexus, according to police.
The Lexus, which was being driven by a man, was also carrying the man's wife and their 14-year-old son.
All four victims were taken to local hospitals, police said.
The driver of the Lexus and his wife both suffered injuries not considered life-threatening, according to police.
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The 14-year-old boy and the 25-year-old driver were both pronounced dead a short while later. Their identities have not been released.
Investigators believe the deceased driver of the Chevy may have been driving while under the influence of alcohol.
The collision marks the city's 47th fatal collision this year, police said.