Science:发现与肌萎缩性侧索硬化有关基因变异

在2月28日《科学》（Science）杂志的在线版上，研究人员报道说，已经找到了一种与某些病例的肌萎缩性侧索硬化（ALS，也被称为Lou Gehrig氏病）相关的罕见基因变异。这些发现可能会帮助研究人员，更多地了解这一致命的成年时起病的运动神经元疾病的发展过程。该疾病中有5-10%的病例是有遗传性的（其他病例的发病原因尚不清楚）。

Jemeen Sreedharan及其在英国和澳大利亚的同僚对英国的一个遗传性ALS的大家族进行了分析。他们在一个叫做TDP-43的基因中发现了一种变异，而该变异看来与该疾病有关。研究人员在受ALS影响的神经元中发现了团簇状的TDP-43蛋白，而这些结果进一步加强了TDP-43与该疾病之间的关联性。

生物谷推荐原始出处：

（Science），DOI: 10.1126/science.1154584，Jemeen Sreedharan，Christopher E. Shaw

TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis

Jemeen Sreedharan , Ian P. Blair , Vineeta B. Tripathi , Xun Hu , Caroline Vance , Boris Rogelj , Steven Ackerley , Jennifer C. Durnall , Kelly L. Williams , Emanuele Buratti , Francisco Baralle , Jacqueline de BelleRoche , J. Douglas Mitchell , P. Nigel Leigh , Ammar Al-Chalabi , Christopher C. Miller , Garth Nicholson , Christopher E. Shaw

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterised pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain and a mechanistic role in neurodegeneration remains speculative. We identified neighbouring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented more readily than wild-type in vitro and caused neural apoptosis and developmental delay in the chick embryo in vivo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.