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Lincoln’s gait, errant gene

Yale Medicine Magazine, 2010 - Autumn


Abraham Lincoln’s gawky gait may have been the result of a neurodegenerative disorder that causes a loss of coordination in the hands and arms and that he likely inherited from his paternal grandparents. Now, a Yale-led study published in March inProceedings of the National Academy of Sciences has revealed the process by which a genetic mutation causes the disorder, spinocerebellar ataxia type 5 (SCA5).

Investigators at Yale, Harvard, and the Jackson Laboratories removed the protein beta-3 spectrin, previously identified as the cause of SCA5, from mouse brains. Without the protein, they found, neurotransmitter receptors and transporters fail to assemble properly in brain regions involving coordination, memory, and cognitive functions.

“Given the widespread distribution of various spectrins in all cells and tissues, we now suspect that several other neurologic diseases, as well as diseases involving other organs, may arise from defects in beta-3 spectrin,” said senior author Jon S. Morrow, Ph.D., M.D. ’76, HS ’79, FW ’81, Raymond Yesner Professor of Pathology and professor of molecular, cellular, and developmental biology.

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