Brown researchers trace brain disorder to DNA mutation

The research team continues to investigate hypotheses regarding the metabolic pathways and how they regulate brain functions.
The research team continues to investigate hypotheses regarding the metabolic pathways and how they regulate brain functions. | File photo
Brown University researchers led by Dr. Eric Morrow, an associate professor in the Warren Alpert Medical School, published their study of two families in Pakistan and Oman whose children suffer from a rare neurological disease in the Proceedings of the National Academy of Sciences recently.

They traced the disease to a mutation in the GPT2 gene. Mutations in GPT2 result in reduced enzyme activity. That enzyme appears essential in developing metabolic pathways in the mitochondria.

When researchers developed and tested mice with a GPT2 enzyme deficiency, they found abnormal brain metabolisms. The mice showed reduced neural and brain growth, and developed fewer connections between synapses.

The engineered mice reflected the children's symptoms, with below-normal brain growth, developmental disabilities and a loss of motor control. Most of the children were able to walk, but developed spastic paraplegia as they grew older, resulting in the loss of the ability to walk.

The research team continues to investigate hypotheses regarding the metabolic pathways and how they regulate brain functions. They are looking forward to testing methods of intervention to prevent progression of the children's condition.

Morrow, David Housman at MIT and Ganeshwaran Mochida at Boston Children's Hospital were the co-corresponding authors. The co-lead authors of the study were investigator Qing Ouyang of Brown and researcher Tojo Nakayama of Boston Children's Hospital.

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