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SHR Neuro Krebs Kardio Lipid

Cullup, T; Kho, AL; Dionisi-Vici, C; Brandmeier, B; Smith, F; Urry, Z; Simpson, MA; Yau, S; Bertini, E; McClelland, V; Al-Owain, M; Koelker, S; Koerner, C; Hoffmann, GF; Wijburg, FA; ten Hoedt, AE; Rogers, RC; Manchester, D; Miyata, R; Hayashi, M; Said, E; Soler, D; Kroisel, PM; Windpassinger, C; Filloux, FM; Al-Kaabi, S; Hertecant, J; Del Campo, M; Buk, S; Bodi, I; Goebel, HH; Sewry, CA; Abbs, S; Mohammed, S; Josifova, D; Gautel, M; Jungbluth, H; .
Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy.
Nat Genet. 2013; 45(1):83-87 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Kroisel Peter
Windpassinger Christian
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Number of Figures: 4
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Abstract:
Vici syndrome is a recessively inherited multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. To investigate the molecular basis of Vici syndrome, we carried out exome and Sanger sequence analysis in a cohort of 18 affected individuals. We identified recessive mutations in EPG5 (previously KIAA1632), indicating a causative role in Vici syndrome. EPG5 is the human homolog of the metazoan-specific autophagy gene epg-5, encoding a key autophagy regulator (ectopic P-granules autophagy protein 5) implicated in the formation of autolysosomes. Further studies showed a severe block in autophagosomal clearance in muscle and fibroblasts from individuals with mutant EPG5, resulting in the accumulation of autophagic cargo in autophagosomes. These findings position Vici syndrome as a paradigm of human multisystem disorders associated with defective autophagy and suggest a fundamental role of the autophagy pathway in the immune system and the anatomical and functional formation of organs such as the brain and heart.
Find related publications in this database (using NLM MeSH Indexing)
Agenesis of Corpus Callosum - genetics
Antigens, Neoplasm - genetics
Autophagy - genetics
Biopsy -
Cataract - genetics
Consanguinity -
Exome -
Family -
Genes, Recessive -
Humans -
Lysosomes - metabolism
Muscle, Skeletal - pathology Muscle, Skeletal - ultrastructure
Mutation -
Proteins - metabolism

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