Rare copy number variations containing genes involved in RASopathies: deletion of SHOC2 and duplication of PTPN11.
Rare copy number variations containing genes involved in RASopathies: deletion of SHOC2 and duplication of PTPN11.
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含有与 RASopathies 相关的基因的罕见拷贝数变异：SHOC2 缺失和 PTPN11 重复
DOI：
10.1186/1755-8166-7-28
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发表时间：
2014
影响因子：
1.3
通讯作者：
Tan ZP
中科院分区：
文献类型：
--
作者：
Chen JL;Zhu X;Zhao TL;Wang J;Yang YF;Tan ZP
背景：Rasopathies是一组与Noonan综合征相关的疾病，具有RAS丝裂原活化蛋白激酶(MAPK)信号通路的异常。努南综合征(NS，OMIM#163950)是一种既有表型又有遗传变异的疾病。我们和其他研究人员已经证明了一小部分RAS疾病患者的拷贝数变异。结果：在12例临床特征为先天性心脏病(CHD)的患者中，我们进行了Illumina SNP阵列分析以确定致病拷贝数变异(Human660W-四芯片、珠台扫描仪和GenomeStudio V2011软件)。我们鉴定了两个罕见的拷贝数变异，它们含有与Ras-MAPK信号通路有关的基因。一个是包含PTPN11的12q24.1-24.3的24Mb复制，另一个是包括SHOC2的10q25.2的183kb缺失。用定量聚合酶链式反应(QPCR)进一步验证了SNP阵列的结果。这可能是首次报道SHOC2单倍体缺失可导致Rasopath样表型。结论：我们的研究结果进一步支持了含有RAS/MAPK通路致病基因的拷贝数变异在Rasopathy或相关疾病中的作用不大。我们建议在Noonan综合征类患者中使用微阵列，这些患者的致病基因没有已确定的突变。
Background:RASopathies are a group of disorders related to Noonan syndrome that with dysregulated RAS-mitogen-activated protein kinase (MAPK) signaling pathway. Noonan syndrome (NS, OMIM# 163950) is a both phenotypically and genotypically variable disorder. We and other researchers have demonstrated that copy number variations underlie a small percentage of patients with RASopathies.Results:In a cohort of 12 clinically characterized patients with congenital heart defect (CHD) and features suggestive of Noonan syndrome or Noonan like syndrome without known causative gene mutation, we performed an Illumina SNP-array analysis to identify the pathogenic copy number variations (Human660W-Quad Chip, Beadstation Scanner and GenomeStudio V2011 software). We identifed two rare copy number variations harboring genes involved in RAS- MAPK signaling pathway of RASopathy. One is a 24 Mb duplication of 12q24.1-24.3 containing PTPN11 and the other is a 183 kb deletion of 10q25.2 including SHOC2. The SNP-array results were further validated by quantitative PCR (qPCR). This is might be the first report suggesting that haploinsufficiency of SHOC2 can result in a RASopathy-like phenotype.Conclusions:Our findings provide additional support that copy number variations containing disease-causing genes of RAS/MAPK pathway play a minor role in RASopathies or related disorders. We recommend the use of microarrays in Noonan syndrome like patients without identified mutations in the causative genes.
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PTPN11 的基因组重复是努南综合征的一个罕见原因。
影响因子：
2
作者：
Graham, John M., Jr.;Kramer, Nancy;Bejjani, Bassem A.;Thiel, Christian T.;Carta, Claudio;Neri, Giovanni;Tartaglia, Marco;Zenker, Martin
通讯作者：
Zenker, Martin
影响因子：
4
作者：
Scheidecker S;Etard C;Pierce NW;Geoffroy V;Schaefer E;Muller J;Chennen K;Flori E;Pelletier V;Poch O;Marion V;Stoetzel C;Strähle U;Nachury MV;Dollfus H
通讯作者：
Dollfus H
影响因子：
30.8
作者：
Cordeddu, Viviana;Di Schiavi, Elia;Pennacchio, Len A.;Ma'ayan, Avi;Sarkozy, Anna;Fodale, Valentina;Cecchetti, Serena;Cardinale, Alessio;Martin, Joel;Schackwitz, Wendy;Lipzen, Anna;Zampino, Giuseppe;Mazzanti, Laura;Digilio, Maria C.;Martinelli, Simone;Flex, Elisabetta;Lepri, Francesca;Bartholdi, Deborah;Kutsche, Kerstin;Ferrero, Giovanni B.;Anichini, Cecilia;Selicorni, Angelo;Rossi, Cesare;Tenconi, Romano;Zenker, Martin;Merlo, Daniela;Dallapiccola, Bruno;Iyengar, Ravi;Bazzicalupo, Paolo;Gelb, Bruce D.;Tartaglia, Marco
通讯作者：
Tartaglia, Marco
影响因子：
9.8
作者：
Martinelli, Simone;De Luca, Alessandro;Tartaglia, Marco
通讯作者：
Tartaglia, Marco
影响因子：
3.5
作者：
Zhu, Xin;Zhang, Yi;Tan, Zhi-Ping
通讯作者：
Tan, Zhi-Ping