Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome.
Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome.
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DOI：
10.1038/ng.1083
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发表时间：
2012-02-26
期刊：
影响因子：
30.8
通讯作者：
Ghevaert, Cedric
中科院分区：
文献类型：
--
作者：
Albers, Cornelis A.;Paul, Dirk S.;Schulze, Harald;Freson, Kathleen;Stephens, Jonathan C.;Smethurst, Peter A.;Jolley, Jennifer D.;Cvejic, Ana;Kostadima, Myrto;Bertone, Paul;Breuning, Martijn H.;Debili, Najet;Deloukas, Panos;Favier, Remi;Fiedler, Janine;Hobbs, Catherine M.;Huang, Ni;Hurles, Matthew E.;Kiddle, Graham;Krapels, Ingrid;Nurden, Paquita;Ruivenkamp, Claudia A. L.;Sambrook, Jennifer G.;Smith, Kenneth;Stemple, Derek L.;Strauss, Gabriele;Thys, Chantal;van Geet, Chris;Newbury-Ecob, Ruth;Ouwehand, Willem H.;Ghevaert, Cedric
外显子连接复合体(EJC)执行必要的RNA处理任务。在这里，我们描述了第一例人类疾病，缺乏半径的血小板减少症(TAR)，由四个EJC亚基中的一个缺乏引起。一种罕见的零等位基因和RBM8A调节区两个低频SNP之一的复合遗传机制导致了TAR。RBM8A编码EJC的Y14亚基。我们发现，这一机制解释了55例罕见的先天性畸形综合征中的53例(P<；5×10−)。其中51例携带先前相关的1q21.1亚微观缺失；两例携带RBM8A的截断或移码零突变。我们发现这两个调节性SNPs在体外导致RBM8A转录减少，并且在TAR病例的血小板中Y14的表达减少。我们的数据表明，Y14功能不全和EjC缺陷可能是TAR综合征的原因。
The exon-junction complex (EJC) performs essential RNA processing tasks. Here, we describe the first human disorder, Thrombocytopenia with Absent Radii (TAR), caused by deficiency in one of the four EJC subunits. A compound inheritance mechanism of a rare null allele and one of two low-frequency SNPs in the regulatory regions of RBM8A, encoding the Y14 subunit of EJC, causes TAR. We found that this mechanism explained 53 of 55 cases (P<5×10−228) with the rare congenital malformation syndrome. Fifty-one of those 53 carried a previously associated submicroscopic deletion of 1q21.1; two carried a truncation or frameshift null mutation in RBM8A. We show that the two regulatory SNPs result in reduction of RBM8A transcription in vitro and that Y14 expression is reduced in platelets from TAR cases. Our data implicate Y14 insufficiency, and presumably EJC defect, as the cause of TAR syndrome.
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COLAUS研究：一项基于人群的研究，旨在研究心血管危险因素和代谢综合征的流行病学和遗传决定因素。
影响因子：
2.1
作者：
Firmann, Mathieu;Mayor, Vladimir;Vidal, Pedro Marques;Bochud, Murielle;Pecoud, Alain;Hayoz, Daniel;Paccaud, Fred;Preisig, Martin;Song, Kijoung S.;Yuan, Xin;Danoff, Theodore M.;Stirnadel, Heide A.;Waterworth, Dawn;Mooser, Vincent;Waeber, Gerard;Vollenweider, Peter
通讯作者：
Vollenweider, Peter
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
5.8
作者：
Morgan, Martin;Anders, Simon;Gentleman, Robert
通讯作者：
Gentleman, Robert
影响因子：
2.5
作者：
Haremaki, Tomomi;Sridharan, Jyotsna;Weinstein, Daniel C.
通讯作者：
Weinstein, Daniel C.
影响因子：
20.3
作者：
Freson, K;Devriendt, K;Van Geet, C
通讯作者：
Van Geet, C