title: SKIV2L mutations cause syndromic diarrhea, or trichohepatoenteric syndrome.
abstract: 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.
authors.affiliation: UMR_S 910, Inserm-Faculté de Médecine, Aix-Marseille Université, Marseille, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fabre
authors.forename: Bernard
authors.initials: B
authors.lastname: Charroux
authors.forename: Christine
authors.initials: C
authors.lastname: Martinez-Vinson
authors.forename: Bertrand
authors.initials: B
authors.lastname: Roquelaure
authors.forename: Egritas
authors.initials: E
authors.lastname: Odul
authors.forename: Ersin
authors.initials: E
authors.lastname: Sayar
authors.forename: Hilary
authors.initials: H
authors.lastname: Smith
authors.forename: Virginie
authors.initials: V
authors.lastname: Colomb
authors.forename: Nicolas
authors.initials: N
authors.lastname: Andre
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hugot
authors.forename: Olivier
authors.initials: O
authors.lastname: Goulet
authors.forename: Caroline
authors.initials: C
authors.lastname: Lacoste
authors.forename: Jacques
authors.initials: J
authors.lastname: Sarles
authors.forename: Julien
authors.initials: J
authors.lastname: Royet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Levy
authors.forename: Catherine
authors.initials: C
authors.lastname: Badens
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D003968:Diarrhea, Infantile / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; C550452:TTC37 protein, human; D004265:DNA Helicases; C114718:SKIV2L protein, human