1、UPF2致病突变携带患者体内的NMD功能失调,病人均有语言功能障碍Costa-mattioli组的合作者在英国与澳大利亚发现并诊断了三个来自独立家庭的患者,三为患者均携带UPF2基因的致病突变(其中案例1和案例2为frameshift突变,案例3携带UPF2的删除突变)。该三名患者的共同症状突出为智能障碍及语言功能障碍,其中包括表述、阅读和拼写等交流功能障碍,诊断描述见下表。(A) Summary of clinical phenotypes in affectedindividuals with UPF2 variants. R, right; AVSD, atrioventricular septal defect;ASD, autism spectrum disorder; N, not present; Y, present; avg, average; ext,extremely; artic, articulation disorder; mod, moderate; NA, not availablebecause the child has severe ID and is non-verbal.研究者通过对病人提取的淋巴细胞细胞系DNA测序结果与先前报道的UPF3B病人和UPF2拷贝数目变异病人的序列【10, 12, 13】进行相关性分析,发现这些病人与UPF3B的基因变化非常相关,并且这三个病人序列之间都呈现较高的相互相关性(如下图),这提示NMD在该三名患者体内均功能失调。(注意,UPF3B在X染色体上表达,所以本研究所引用的UPF3B致病突变男性患者为先天性NMD因子UPF3B knockout,因此,其基因数据是一个非常具有代表性的NMD失调的基因序列组。)
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