GENETICS: Four Score and Nine Generations Ago

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Science  03 Feb 2006:
Vol. 311, Issue 5761, pp. 581c
DOI: 10.1126/science.311.5761.581c

Neurodegenerative disorders vary in their pathologies, but because they all involve cell death, there is the possibility that they share a common mechanism of pathogenesis. One emerging hypothesis posits that the disorders arise because of defects in the intracellular machinery that transports vesicles and proteins.

Ikeda et al. have studied three families afflicted with spinocerebellar ataxia type 5 (SCA5), a dominantly inherited neurodegenerative disorder characterized by uncoordinated gait and slurred speech. Affected individuals were found to have mutations in the SPTBN2 gene, which encodes β-III spectrin, a cytoskeletal protein that is expressed in Purkinje cells, which are markedly depleted in the brains of individuals with SCA5. β-III spectrin has been implicated previously in protein trafficking, and the mutations may disrupt transport of the neurotransmitter glutamate. Of historical interest, one of the families studied was an 11-generation kindred descended from the paternal grandparents of President Abraham Lincoln. Whether he inherited the SCA5 mutation is unknown, but this discovery may reignite discussions on the ethics of analyzing his DNA. — PAK

Nat. Genet. 10.1038/ng1728 (2006).

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