SKIV2L Mutations Cause Syndromic Diarrhea, or Trichohepatoenteric Syndrome
SKIV2L Mutations Cause Syndromic Diarrhea, or Trichohepatoenteric Syndrome
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DOI：
10.1016/j.ajhg.2012.02.009
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发表时间：
2012-04-06
影响因子：
9.8
通讯作者：
Badens, Catherine
中科院分区：
文献类型：
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作者：
Fabre, Alexandre;Charroux, Bernard;Badens, Catherine
综合征性腹泻（或trichoho肝肠综合征）是一种罕见的先天性肠道疾病，其特征是难治性腹泻和羊毛状毛发，最近发现与TTC37基因突变有关。虽然数据库报告TTC37是酵母Ski-complex辅因子之一sk3p的人类同源物，但这一线索在最初的研究中没有被调查。Ski复合体是外泌体介导的RNA监视所需的多蛋白复合体，包括正常mRNA的调节和无功能mRNA的衰变。考虑到TTC37与Ski3p是同源的，我们在6例没有TTC37变异的典型综合征性腹泻患者中发现了一个编码另一个ski复合体辅助因子SKIV2L的基因。我们在所有六个人身上都发现了突变。我们的研究结果表明，编码人类Ski复合体的辅助因子的基因突变导致综合征性腹泻，建立了人类外泌体复合体缺陷与孟德尔病之间的联系。
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.