Police said they responded to a shooting around 7:30 p.m. Monday and found a boy suffering from a gunshot wound.
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The boy was transported to a hospital, where he died.
An investigation revealed the siblings gained access to an unsecured firearm and one of the siblings accidentally fired the weapon, striking the boy, police said in a news release.
Police said the boys were home alone, loaded the handgun themselves and started playing around with it.
"It turns out that the weapon was possibly unsecured within the residence and the juvenile was able to retrieve the weapon, was playing with it in the residence and pointed it at the victim and accidentally fired a round," said Sgt. John Echevarria with San Bernardino police.
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Police said the mother of the children, identified as 45-year-old Gabriela Keeton, was taken into custody after being contacted at the scene. She is behind bars on suspicion of felony child endangerment.
Officials say the boys' father was in the hospital during the incident for an unrelated medical issue.
San Bernardino police is asking anyone with information to call Detective Reyna at (909) 384-5638 or Sergeant Flores at (909) 384-5659.