Gitcho Michael A, Baloh Robert H, Chakraverty Sumi, Mayo Kevin, Norton Joanne B, Levitch Denise, Hatanpaa Kimmo J, White Charles L, Bigio Eileen H, Caselli Richard, Baker Matt, Al-Lozi Muhammad T, Morris John C, Pestronk Alan, Rademakers Rosa, Goate Alison M, Cairns Nigel J
Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ann Neurol. 2008 Apr;63(4):535-8. doi: 10.1002/ana.21344. Epub 2008 Feb 20.
To identify novel causes of familial neurodegenerative diseases, we extended our previous studies of TAR DNA-binding protein 43 (TDP-43) proteinopathies to investigate TDP-43 as a candidate gene in familial cases of motor neuron disease. Sequencing of the TDP-43 gene led to the identification of a novel missense mutation, Ala-315-Thr, which segregates with all affected members of an autosomal dominant motor neuron disease family. The mutation was not found in 1,505 healthy control subjects. The discovery of a missense mutation in TDP-43 in a family with dominantly inherited motor neuron disease provides evidence of a direct link between altered TDP-43 function and neurodegeneration.
为了确定家族性神经退行性疾病的新病因，我们扩展了之前对TAR DNA结合蛋白43（TDP - 43）蛋白病的研究，以调查TDP - 43作为运动神经元病家族病例中的候选基因。对TDP - 43基因进行测序后发现了一个新的错义突变，即丙氨酸315变为苏氨酸，该突变与一个常染色体显性运动神经元病家族的所有患病成员共分离。在1505名健康对照者中未发现该突变。在一个具有显性遗传运动神经元病的家族中发现TDP - 43的错义突变，为TDP - 43功能改变与神经退行性变之间的直接联系提供了证据。
