De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.
De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.
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DOI：
10.1016/j.ajhg.2018.06.001
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发表时间：
2018-07-05
影响因子：
9.8
通讯作者：
Raymond FL
中科院分区：
文献类型：
--
作者：
Ito Y;Carss KJ;Duarte ST;Hartley T;Keren B;Kurian MA;Marey I;Charles P;Mendonça C;Nava C;Pfundt R;Sanchis-Juan A;van Bokhoven H;van Essen A;van Ravenswaaij-Arts C;NIHR BioResource;Care4Rare Canada Consortium;Boycott KM;Kernohan KD;Dyack S;Raymond FL
近年来，下一代测序在阐明许多智力残疾亚型的遗传病因方面发挥了无价的作用。在这里，使用外显子组测序和全基因组测序，我们确定了三个从头截断突变的WAS蛋白家族成员1（WASF 1）在5个无关的个体中度至重度智力残疾与自闭症特征和癫痫发作。WASF 1，也称为WAVE 1，是WAVE复合物的一部分，并作为Rac-GTdR和肌动蛋白之间的介体，以诱导肌动蛋白聚合。通过Matchmaker Exchange连接的三个突变是c.1516C>T（p.Arg506Ter），其发生在三个无关个体中，c.1558C>T（p.Gln520Ter）和c.1482delinsGCCAGG（p.Ile494MetfsTer23）。所有这三种变体都被预测部分或完全破坏C-末端肌动蛋白结合WCA结构域。使用来自两个患有c.1516C>T突变的受影响个体的成纤维细胞进行的功能研究显示了截短的WASF 1和肌动蛋白重塑的缺陷。这项研究提供的证据表明，在WASF 1从头杂合突变导致一种罕见的智力残疾。
Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability.
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肌动蛋白调节波复合物的结构和控制。
影响因子：
64.8
作者：
Chen, Zhucheng;Borek, Dominika;Padrick, Shae B.;Gomez, Timothy S.;Metlagel, Zoltan;Ismail, Ayman M.;Umetani, Junko;Billadeau, Daniel D.;Otwinowski, Zbyszek;Rosen, Michael K.
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影响因子：
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作者：
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通讯作者：
Takenawa, T
影响因子：
4.5
作者：
Hamdan FF;Srour M;Capo-Chichi JM;Daoud H;Nassif C;Patry L;Massicotte C;Ambalavanan A;Spiegelman D;Diallo O;Henrion E;Dionne-Laporte A;Fougerat A;Pshezhetsky AV;Venkateswaran S;Rouleau GA;Michaud JL
通讯作者：
Michaud JL
影响因子：
64.5
作者：
Li, Z;Okamoto, K;Sheng, M
通讯作者：
Sheng, M