We report on a sibling pair with the EPG5 c.1007A > G mutation who developed a severe form of Vici syndrome and died in infancy. The c.1007A > G (p.Gln336Arg) mutation, affecting the penultimate nucleotide and the splicing of exon 2 is the most common mutation of EPG5 and is typically associated with a less devastating prognosis: cardiomyopathy and cataract are less frequent consequences and the median survival time is 78 months compared to an overall median survival of 42 months. The less severe course related to c.1007A > G was formerly explained by the preserved canonical splicing in 25% of the transcripts. In contrast, we found the messenger RNA encoded by the c.1007A > G allele to be absent, explaining the severe course of the disease. This family provides another example of phenotypic variability related to a differential splicing.

中文翻译：

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EPG5 c.1007A > G 突变在患有快速进展的 Vici 综合征的同胞对中

我们报告了一对具有 EPG5 c.1007A > G 突变的兄弟姐妹，他们患有严重的 Vici 综合征并在婴儿期死亡。c.1007A > G (p.Gln336Arg) 突变，影响倒数第二个核苷酸和外显子 2 的剪接是 EPG5 最常见的突变，通常与破坏性较小的预后相关：心肌病和白内障是不太常见的后果，中位数生存时间为 78 个月，而总体中位生存期为 42 个月。与 c.1007A > G 相关的不太严重的过程以前是通过 25% 的转录本中保留的规范剪接来解释的。相比之下，我们发现由 c.1007A > G 等位基因编码的信使 RNA 不存在，这解释了该病的严重过程。