Molecular pathogenesis of myotonic dystrophy in the central nervous system

我们发现，选择性剪接因子，muscleblind-like 1（MBNL 1）和MBNL 2的核隔离解释了在人类强直性肌营养不良1型（DM 1）大脑中观察到的剪接缺陷，MBNL 2的贡献大于MBNL 1。我们在DM 1患者的额叶皮质、颞叶皮质和海马中发现了类似的剪接缺陷，但在小脑中没有发现。这可能是最短的CTG重复扩增可能有助于在DM 1小脑剪接缺陷的缺乏。DMPK蛋白表达减少可能与DM 1小脑组织未发现病理异常有关。

We showed that nuclear sequestration of alternative splicing factors, muscleblind-like 1 (MBNL1) and MBNL2 explains splicing defects observed in human myotonic dystrophy type 1 (DM1) brain and the contribution of MBNL2 is greater than that of MBNL1. We found similar splicing defects in frontal cortex, temporal cortex, and hippocampus, but not in cerebellum from DM1 patients. It is probable that the shortest CTG repeat expansion could contribute to the lack of splicing defects in DM1 cerebellum. Also, the less expression of DMPK protein might be related with the fact that pathological abnormalities were not found in the DM1 cerebellum.