EPG5 c.1007A > G mutation in a sibling pair with rapidly progressing Vici syndrome

• Published in: Annals of human genetics Vol. 84; no. 1; pp. 80 - 86
• Main Authors: Vojcek, Eszter, Keszthelyi, Tália Magdolna, Jávorszky, Eszter, Balogh, Lídia, Tory, Kálmán
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-01-2020
• Subjects: Adolescent; Agenesis of Corpus Callosum - genetics; Agenesis of Corpus Callosum - pathology; Autophagy-Related Proteins - genetics; Cardiomyopathy; Cataract - genetics; Cataract - pathology; differential splicing; Disease Progression; Female; Genetic variability; Gln336Arg; Humans; Infant; Infant, Newborn; Male; Medical prognosis; mRNA; Mutation; phenotype variability; Prognosis; RNA Splicing; Siblings; Splicing; Survival; Survival Rate; Vesicular Transport Proteins - genetics; Vici syndrome; phenotype variability; differential splicing; Vici syndrome; Gln336Arg
• ISSN: 0003-4800; 1469-1809
• DOI: 10.1111/ahg.12337

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.