SKIV2L Mutations Cause Syndromic Diarrhea, or Trichohepatoenteric Syndrome

Syndromic diarrhea (or trichohepatoenteric syndrome) is a rare congenital bowel disorder characterized by intractable diarrhea and woolly hair, and it has recently been associated with mutations in TTC37. Although databases report TTC37 as being the human ortholog of Ski3p, one of the yeast Ski-comp...

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Bibliographic Details
Published in:American journal of human genetics 2012-04, Vol.90 (4), p.689-692
Main Authors: Fabre, Alexandre, Charroux, Bernard, Martinez-Vinson, Christine, Roquelaure, Bertrand, Odul, Egritas, Sayar, Ersin, Smith, Hilary, Colomb, Virginie, Andre, Nicolas, Hugot, Jean-Pierre, Goulet, Olivier, Lacoste, Caroline, Sarles, Jacques, Royet, Julien, Levy, Nicolas, Badens, Catherine
Format: Article
Language:English
Subjects:
Biological and medical sciences
Carrier Proteins
Carrier Proteins - genetics
Cellular Biology
Cofactors
Congenital diseases
Diarrhea
Diarrhea, Infantile
Diarrhea, Infantile - genetics
DNA Helicases
DNA Helicases - genetics
exosomes
Fundamental and applied biological sciences. Psychology
Gastroenterology. Liver. Pancreas. Abdomen
General aspects. Genetic counseling
Genetics
Genetics of eukaryotes. Biological and molecular evolution
Hair
Humans
Infant
Infant, Newborn
Intestine
Lead
Life Sciences
Medical genetics
Medical sciences
Molecular and cellular biology
mRNA
mRNA turnover
Mutation
Other diseases. Semiology
RNA-protein interactions
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Syndrome
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Summary:Syndromic diarrhea (or trichohepatoenteric syndrome) is a rare congenital bowel disorder characterized by intractable diarrhea and woolly hair, and it has recently been associated with mutations in TTC37. Although databases report TTC37 as being the human ortholog of Ski3p, one of the yeast Ski-complex cofactors, this lead was not investigated in initial studies. The Ski complex is a multiprotein complex required for exosome-mediated RNA surveillance, including the regulation of normal mRNA and the decay of nonfunctional mRNA. Considering the fact that TTC37 is homologous to Ski3p, we explored a gene encoding another Ski-complex cofactor, SKIV2L, in six individuals presenting with typical syndromic diarrhea without variation in TTC37. We identified mutations in all six individuals. Our results show that mutations in genes encoding cofactors of the human Ski complex cause syndromic diarrhea, establishing a link between defects of the human exosome complex and a Mendelian disease.
ISSN:0002-9297
1537-6605
DOI:10.1016/j.ajhg.2012.02.009