Phenotypic and molecular convergence of 2q23.1 deletion syndrome with other neurodevelopmental syndromes associated with autism spectrum disorder.
Phenotypic and molecular convergence of 2q23.1 deletion syndrome with other neurodevelopmental syndromes associated with autism spectrum disorder.
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2q23.1 缺失综合征与其他与自闭症谱系障碍相关的神经发育综合征的表型和分子趋同。
DOI：
10.3390/ijms16047627
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发表时间：
2015-04-07
影响因子：
5.6
通讯作者：
Elsea SH
中科院分区：
文献类型：
--
作者：
Mullegama SV;Alaimo JT;Chen L;Elsea SH
大约20%的自闭症谱系障碍（ASD）是具有明确遗传原因的综合征。研究相关基因可以深入了解ASD的分子和细胞机制。2q23.1缺失综合征（2q23.1 deletion syndrome，MBD 5）是近年来发现的一种与ASD相关的遗传性神经发育障碍。在ASD队列中发现了MBD 5的突变。在这项研究中，我们提供了2q23.1缺失综合征的流行特征的表型更新，其中包括严重的智力残疾，癫痫发作，显著的语言障碍，睡眠障碍和自闭症样行为问题。接下来，我们研究了9种与ASD相关的神经发育障碍之间的表型、分子和网络/通路关系：2q23.1缺失Rett、Angelman、Pitt-Hopkins、2q23.1重复、5q14.3缺失、Kleefstra、Kabuki化妆和Smith-Magenis综合征。我们发现表型重叠，包括智力残疾，语言延迟，癫痫发作，睡眠障碍，张力减退，和自闭症样行为。在分子水平上，MBD 5可能调控UBE 3A、TCF 4、MEF 2C、EHMT 1和RAI 1的表达。网络分析表明，可能存在间接的蛋白质相互作用，进一步暗示这些基因在共同途径中的功能。此外，我们表明，当MBD 5和RAI 1是单倍不足，他们扰乱了几个共同的途径，与神经元和行为的发展。这些发现支持进一步研究与神经发育障碍和ASD相关的基因之间的分子和途径关系，这将有望导致可能针对治疗干预的共同调控点。
Roughly 20% of autism spectrum disorders (ASD) are syndromic with a well-established genetic cause. Studying the genes involved can provide insight into the molecular and cellular mechanisms of ASD. 2q23.1 deletion syndrome (causative gene, MBD5) is a recently identified genetic neurodevelopmental disorder associated with ASD. Mutations in MBD5 have been found in ASD cohorts. In this study, we provide a phenotypic update on the prevalent features of 2q23.1 deletion syndrome, which include severe intellectual disability, seizures, significant speech impairment, sleep disturbance, and autistic-like behavioral problems. Next, we examined the phenotypic, molecular, and network/pathway relationships between nine neurodevelopmental disorders associated with ASD: 2q23.1 deletion Rett, Angelman, Pitt-Hopkins, 2q23.1 duplication, 5q14.3 deletion, Kleefstra, Kabuki make-up, and Smith-Magenis syndromes. We show phenotypic overlaps consisting of intellectual disability, speech delay, seizures, sleep disturbance, hypotonia, and autistic-like behaviors. Molecularly, MBD5 possibly regulates the expression of UBE3A, TCF4, MEF2C, EHMT1 and RAI1. Network analysis reveals that there could be indirect protein interactions, further implicating function for these genes in common pathways. Further, we show that when MBD5 and RAI1 are haploinsufficient, they perturb several common pathways that are linked to neuronal and behavioral development. These findings support further investigations into the molecular and pathway relationships among genes linked to neurodevelopmental disorders and ASD, which will hopefully lead to common points of regulation that may be targeted toward therapeutic intervention.
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影响因子：
3.7
作者：
Du Y;Liu B;Guo F;Xu G;Ding Y;Liu Y;Sun X;Xu G
通讯作者：
Xu G
MBD5的破坏有助于一系列精神病理学和神经发育异常。
影响因子：
11
作者：
Hodge JC;Mitchell E;Pillalamarri V;Toler TL;Bartel F;Kearney HM;Zou YS;Tan WH;Hanscom C;Kirmani S;Hanson RR;Skinner SA;Rogers RC;Everman DB;Boyd E;Tapp C;Mullegama SV;Keelean-Fuller D;Powell CM;Elsea SH;Morton CC;Gusella JF;DuPont B;Chaubey A;Lin AE;Talkowski ME
通讯作者：
Talkowski ME
影响因子：
5.2
作者：
Chung, Brian H. Y.;Mullegama, Sureni;Mendoza-Londono, Roberto
通讯作者：
Mendoza-Londono, Roberto
影响因子：
3.5
作者：
Banka, S.;Lederer, D.;Donnai, D.
通讯作者：
Donnai, D.
基因组拷贝数变体分析暗示了中国婴儿痉挛儿童的MBD5和HNRNPU基因，并扩大了2q23.1缺失的临床谱。
影响因子：
--
作者：
Du X;An Y;Yu L;Liu R;Qin Y;Guo X;Sun D;Zhou S;Wu B;Jiang YH;Wang Y
通讯作者：
Wang Y