SKIV2L Mutations Cause Syndromic Diarrhea, or Trichohepatoenteric Syndrome

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• 作者：Alexandre Fabre¹ ; ² ; Bernard Charroux³ ; Christine Martinez-Vinson⁴ ; Bertrand Roquelaure² ; Egritas Odul⁵ ; Ersin Sayar⁶ ; Hilary Smith⁷ ; Virginie Colomb⁸ ; Nicolas Andre⁹ ; Jean-Pierre Hugot⁴ ; Olivier Goulet⁸ ; Caroline Lacoste¹⁰ ; Jacques Sarles² ; Julien Royet³ ; Nicolas Levy¹ ; ¹⁰ ; Catherine Badens¹ ; ¹⁰ ; ^{catherine.badens@ap-hm.fr}
• 刊名：The American Journal of Human Genetics
• 出版年：2012
• 出版时间：6 April, 2012
• 年：2012
• 卷：90
• 期：4
• 页码：689-692
• 全文大小：307 K

文摘

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.