Department of Neurogenetics, UCL Institute of Neurology, Queen Square House, University College London, London, United Kingdom; School of Biological Sciences, University of the Punjab, Lahore, Pakistan.
Khawaja Muhammad Safdar Medical College, Sialkot, Pakistan.
Gene. 2021 Mar 1;771:145360. doi: 10.1016/j.gene.2020.145360. Epub 2020 Dec 15.
Variants in SETX have been implicated in recessively and dominantly inherited disorders, ataxia with oculomotor apraxia type 2 (AOA2 OMIM# 606002) and amyotrophic lateral sclerosis (ALS4, OMIM# 602433) respectively, in humans. We report two novel bi-allelic pathogenic variants in SETX in patients suffering from ataxia with oculomotor apraxia type 2, extending the allelic spectrum of the gene variants. We also discuss the pathogenicity of SETX variants in relation to the evolutionary conservation status of the affected amino acids. Our analyses suggest that variants of some amino acids which are not fully conserved in evolution, may cause a disorder in humans, provided the particular pathogenic variant is absent in other orthologues.
SETX 中的变异已分别在人类中被牵连到隐性和显性遗传疾病中，即眼动运动性共济失调 2 型（AOA2 OMIM#606002）和肌萎缩侧索硬化症（ALS4，OMIM#602433）。我们报道了两位患有眼动运动性共济失调 2 型的患者的 SETX 中两个新的双等位基因致病性变异，扩展了该基因变异的等位基因谱。我们还讨论了 SETX 变异与受影响氨基酸的进化保守状态的相关性。我们的分析表明，在进化中不完全保守的某些氨基酸的变异可能会导致人类疾病，前提是特定的致病变异在其他同源物中不存在。
