Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7.
Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7.
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DOI：
10.1038/s41436-020-0792-7
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
Gordon CT
中科院分区：
文献类型：
--
作者：
Castilla-Vallmanya L;Selmer KK;Dimartino C;Rabionet R;Blanco-Sánchez B;Yang S;Reijnders MRF;van Essen AJ;Oufadem M;Vigeland MD;Stadheim B;Houge G;Cox H;Kingston H;Clayton-Smith J;Innis JW;Iascone M;Cereda A;Gabbiadini S;Chung WK;Sanders V;Charrow J;Bryant E;Millichap J;Vitobello A;Thauvin C;Mau-Them FT;Faivre L;Lesca G;Labalme A;Rougeot C;Chatron N;Sanlaville D;Christensen KM;Kirby A;Lewandowski R;Gannaway R;Aly M;Lehman A;Clarke L;Graul-Neumann L;Zweier C;Lessel D;Lozic B;Aukrust I;Peretz R;Stratton R;Smol T;Dieux-Coëslier A;Meira J;Wohler E;Sobreira N;Beaver EM;Heeley J;Briere LC;High FA;Sweetser DA;Walker MA;Keegan CE;Jayakar P;Shinawi M;Kerstjens-Frederikse WS;Earl DL;Siu VM;Reesor E;Yao T;Hegele RA;Vaske OM;Rego S;Undiagnosed Diseases Network, Care4Rare Canada Consortium;Shapiro KA;Wong B;Gambello MJ;McDonald M;Karlowicz D;Colombo R;Serretti A;Pais L;O'Donnell-Luria A;Wray A;Sadedin S;Chong B;Tan TY;Christodoulou J;White SM;Slavotinek A;Barbouth D;Morel Swols D;Parisot M;Bole-Feysot C;Nitschké P;Pingault V;Munnich A;Cho MT;Cormier-Daire V;Balcells S;Lyonnet S;Grinberg D;Amiel J;Urreizti R;Gordon CT
肿瘤坏死因子受体相关因子7 （TRAF7）的体细胞变异导致脑膜瘤，而最近在7例发育迟缓和心脏、面部和手指异常的患者中发现了种系变异。我们的目标是在大量患者中确定与TRAF7种系变异相关的临床和突变谱，并通过对患者成纤维细胞的转录组学分析确定这些变异的分子效应。我们在多个独立的诊断或研究中心对未确诊的发育障碍患者进行了外显子组、靶向捕获和Sanger测序。表型和突变比较通过数据交换平台进行。对来自患者和对照组的成纤维细胞的RNA进行全转录组测序。我们在45例患者中发现TRAF7的杂合错义变异是导致发育迟缓-畸形综合征的原因。主要特征包括可识别的面部完形（尤其是眼睑下垂）、短颈、胸突、指偏和动脉导管未闭。几乎所有的变异都发生在WD40重复序列中，并且大多数是复发性的。在患者成纤维细胞中发现了几个差异表达的基因。我们首次提供了与TRAF7发育综合征相关的临床和突变谱的大规模分析，并通过转录组研究阐明了其分子病因。
Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. We performed exome, targeted capture and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially-expressed genes were identified in patient fibroblasts. We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies.
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DOI：
10.1038/modpathol.2017.153
发表时间：
2018-04
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
Goode B;Joseph NM;Stevers M;Van Ziffle J;Onodera C;Talevich E;Grenert JP;Yeh I;Bastian BC;Phillips JJ;Garg K;Rabban JT;Zaloudek C;Solomon DA
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Solomon DA
DOI：
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发表时间：
2002-04-16
影响因子：
11.1
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15.9
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影响因子：
4.2
作者：
Wang, Lixin;Wang, Lei;Liu, Sijin
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影响因子：
50.3
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通讯作者：
de Sauvage FJ