EPG5 c.1007A > G mutation in a sibling pair with rapidly progressing Vici syndrome. (11th June 2019)

• Record Type: Journal Article
• Authors: Vojcek, Eszter; Keszthelyi, Tália Magdolna; Jávorszky, Eszter; Balogh, Lídia; Tory, Kálmán
• Is Part Of: Annals of human genetics. Volume 84:Number 1(2020:Jan.)
• Page Start: 80
• Page End: 86
• Publication Date: 2019-06-11
• Subjects: differential splicing -- Gln336Arg -- phenotype variability -- Vici syndrome; Human genetics -- Periodicals; 599.935
• DOI: 10.1111/ahg.12337
• Languages: English
• ISSNs: 0003-4800

Abstract

Abstract: 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.