Neurogenetics Group, Center for Molecular Neurology, University of Antwerp, Belgium.
Laboratory of Neuromuscular Pathology, Institute Born-Bunge, University of Antwerp, Belgium.
Brain. 2019 Sep 1;142(9):2605-2616. doi: 10.1093/brain/awz216.
Distal hereditary motor neuropathies are a rare subgroup of inherited peripheral neuropathies hallmarked by a length-dependent axonal degeneration of lower motor neurons without significant involvement of sensory neurons. We identified patients with heterozygous nonsense mutations in the αII-spectrin gene, SPTAN1, in three separate dominant hereditary motor neuropathy families via next-generation sequencing. Variable penetrance was noted for these mutations in two of three families, and phenotype severity differs greatly between patients. The mutant mRNA containing nonsense mutations is broken down by nonsense-mediated decay and leads to reduced protein levels in patient cells. Previously, dominant-negative αII-spectrin gene mutations were described as causal in a spectrum of epilepsy phenotypes.
远端遗传性运动神经病是一组罕见的遗传性周围神经病亚组，其特征是下运动神经元的轴突退行性变呈长度依赖性，而感觉神经元无明显受累。我们通过下一代测序在三个独立的显性遗传性运动神经病家族中发现了杂合无义突变的αII- spectrin 基因（SPTAN1）的患者。在两个家族中的三个突变中，观察到这些突变的可变外显率，并且患者之间的表型严重程度差异很大。含有无义突变的突变 mRNA 通过无义介导的衰变而被破坏，并导致患者细胞中的蛋白水平降低。以前，显性负性αII- spectrin 基因突变被描述为一系列癫痫表型的原因。
