Neuromuscular Unit, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland.
Institute of Biochemistry and Biophysics Polish Academy of Sciences, 02-106 Warsaw, Poland.
Int J Mol Sci. 2022 Aug 31;23(17):9913. doi: 10.3390/ijms23179913.
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a heritable neurodegenerative disease characterized by rapid respiratory failure within the first months of life and progressive muscle weakness and wasting. Although the causative gene, , is well defined, information on mutations is not always sufficient to diagnose particular patients, as the gene is highly polymorphic and the pathogenicity of many gene variants is unknown. In this study, we generated a simple yeast model to establish the significance of variants for disease development, especially those that are missense mutations. We have shown that cDNA of the human gene encodes protein which is functional in yeast cells and different pathogenic mutations affect this functionality. Furthermore, there is a correlation between the phenotype estimated in in vitro studies and our results, indicating that our model may be used to quickly and simply distinguish between pathogenic and non-pathogenic mutations identified in in patients.
1 型脊髓性肌萎缩伴发进行性呼吸系统疾病（SMARD1）是一种遗传性神经退行性疾病，其特征是在生命的最初几个月内迅速发生呼吸衰竭，以及进行性肌肉无力和萎缩。尽管致病基因 已经明确，但并非所有的 突变信息都足以诊断特定的患者，因为该基因高度多态性，许多基因变异的致病性尚不清楚。在这项研究中，我们构建了一个简单的酵母模型，以确定 变体对疾病发展的意义，尤其是那些错义突变。我们已经表明，人类基因的 cDNA 编码的蛋白质在酵母细胞中具有功能，并且不同的致病性突变会影响这种功能。此外，体外研究中估计的表型与我们的结果之间存在相关性，表明我们的模型可用于快速简便地区分在患者 中鉴定出的致病性和非致病性突变。
