Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association.
Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association.
复制标题
DOI：
10.1038/ki.2013.417
复制
发表时间：
2014-06
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
作者：
先天性肾脏和泌尿道异常（CAKUT）约占慢性肾病儿童的一半，是美国儿童终末期肾病的最常见原因。然而，其遗传病因仍然是最难以捉摸的。泌尿系统相关性是一种罕见的疾病，涉及多个器官的先天性异常，包括肾脏和泌尿道，高达60%的病例。通过纯合性定位和全外显子组重测序，结合基于阵列的多重PCR和下一代测序的高通量突变分析，我们在两个孤立CAKUT家族和三个VCANL相关家族中鉴定了TNF受体相关蛋白1（TRAP1）基因的隐性突变。TRAP1是一种热休克蛋白90相关的线粒体伴侣蛋白，可能参与抗凋亡和内质网应激信号传导。Trap1在发育中的小鼠肾脏E13.5的肾上皮细胞和成年大鼠的肾脏中表达，最显著的是在近端小管和亨利氏袢的粗髓升支中。因此，我们确定TRAP1突变极有可能导致CAKUT或CAKUT与VEGIL相关。
Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum-stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle’s loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or CAKUT in VACTERL association.
登录
查看更多内容
影响因子：
64.5
作者：
Chaki M;Airik R;Ghosh AK;Giles RH;Chen R;Slaats GG;Wang H;Hurd TW;Zhou W;Cluckey A;Gee HY;Ramaswami G;Hong CJ;Hamilton BA;Cervenka I;Ganji RS;Bryja V;Arts HH;van Reeuwijk J;Oud MM;Letteboer SJ;Roepman R;Husson H;Ibraghimov-Beskrovnaya O;Yasunaga T;Walz G;Eley L;Sayer JA;Schermer B;Liebau MC;Benzing T;Le Corre S;Drummond I;Janssen S;Allen SJ;Natarajan S;O'Toole JF;Attanasio M;Saunier S;Antignac C;Koenekoop RK;Ren H;Lopez I;Nayir A;Stoetzel C;Dollfus H;Massoudi R;Gleeson JG;Andreoli SP;Doherty DG;Lindstrad A;Golzio C;Katsanis N;Pape L;Abboud EB;Al-Rajhi AA;Lewis RA;Omran H;Lee EY;Wang S;Sekiguchi JM;Saunders R;Johnson CA;Garner E;Vanselow K;Andersen JS;Shlomai J;Nurnberg G;Nurnberg P;Levy S;Smogorzewska A;Otto EA;Hildebrandt F
通讯作者：
Hildebrandt F
影响因子：
1.3
作者：
Smith, Jodi M.;Stablein, Donald M.;McDonald, Ruth A.
通讯作者：
McDonald, Ruth A.
影响因子：
3.7
作者：
Solomon BD
通讯作者：
Solomon BD
影响因子：
30.8
作者：
Zhou, Weibin;Otto, Edgar A.;Hildebrandt, Friedhelm
通讯作者：
Hildebrandt, Friedhelm
影响因子：
5.3
作者：
TENKATE, LP;SCHEFFER, H;CAMPAGNE, JGV
通讯作者：
CAMPAGNE, JGV