title: First description of a patient with Vici syndrome due to a mutation affecting the penultimate exon of EPG5 and review of the literature.
abstract: Vici syndrome is a rare autosomal recessively inherited multisystem disorder characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency, psychomotor delay, and hypopigmentation. Cullup et al. recently identified mutations in the gene EPG5 as the cause of Vici syndrome. EPG5 is involved in autophagy, an evolutionarily conserved lysosomal degradation process that is essential for cell homeostasis. Following the first description in 1988 by Vici et al., 24 other cases of Vici syndrome have been published with variable expression of the defining features. Here, we report on a further case of Vici syndrome with a homozygous truncating mutation of EPG5, identified by whole-exome sequencing. The mutation in our patient is the first reported affecting the penultimate exon of EPG5 and presenting with typical clinical manifestations of Vici syndrome. Additionally, we present a detailed clinical analysis of Vici syndrome comprising all cases previously described in the literature.
authors.affiliation: Institute of Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Ehmke
authors.forename: Nima
authors.initials: N
authors.lastname: Parvaneh
authors.forename: Peter
authors.initials: P
authors.lastname: Krawitz
authors.forename: Mahmoud-Reza
authors.initials: MR
authors.lastname: Ashrafi
authors.forename: Parviz
authors.initials: P
authors.lastname: Karimi
authors.forename: Mehrzad
authors.initials: M
authors.lastname: Mehdizadeh
authors.forename: Ulrike
authors.initials: U
authors.lastname: Krüger
authors.forename: Jochen
authors.initials: J
authors.lastname: Hecht
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
authors.forename: Peter N
authors.initials: PN
authors.lastname: Robinson
mesh_terms: D061085:Agenesis of Corpus Callosum / Q000235:genetics* / Q000473:pathology*; D000071183:Autophagy-Related Proteins; D001483:Base Sequence; D002386:Cataract / Q000235:genetics* / Q000473:pathology*; D059472:Exome / Q000235:genetics; D005091:Exons / Q000235:genetics; D017809:Fatal Outcome; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D007223:Infant; D007492:Iran; D051907:Lysosomal Membrane Proteins; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D033921:Vesicular Transport Proteins
chemical_list: D000071183:Autophagy-Related Proteins; C000592185:EPG5 protein, human; D051907:Lysosomal Membrane Proteins; D011506:Proteins; D033921:Vesicular Transport Proteins
keywords: EPG5; Vici syndrome; agenesis of the corpus callosum, autophagy; cardiomyopathy; developmental delay; hypopigmentation; immunodeficiency; whole-exome sequencing