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的变异体分别与人类的隐性和显性遗传疾病，共济失调伴动眼性失用症2型（AOA2 OMIM＃606002）和肌萎缩性侧索硬化（ALS4，OMIM＃602433）有关。我们在患有共济失调伴动眼性失用症2型的患者中，在SETX中报告了两个新的双等位基因病原体变异，扩展了基因变异的等位基因谱。我们还讨论了与受影响的氨基酸的进化保守状态有关的SETX变体的致病性。我们的分析表明，某些氨基酸的变体在进化中不完全保守，如果其他直系同源物不存在这种特定的致病变体，则可能导致人类疾病。