Mutation in Parkinson disease-associated, G-protein-coupled receptor 37 (GPR37/PaelR) is related to autism spectrum disorder.
Mutation in Parkinson disease-associated, G-protein-coupled receptor 37 (GPR37/PaelR) is related to autism spectrum disorder.
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帕金森氏病相关的G蛋白偶联受体37（GPR37/PAELR）突变与自闭症谱系障碍有关。
DOI：
10.1371/journal.pone.0051155
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Momoi MY
中科院分区：
文献类型：
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作者：
Fujita-Jimbo E;Yu ZL;Li H;Yamagata T;Mori M;Momoi T;Momoi MY
自闭症谱系障碍(ASD)是一种神经发育障碍，其分子发病机制知之甚少。在这里，我们在ASD患者中发现了位于染色体7q31-33上的G蛋白偶联受体37基因(GPR37)的两个突变，称为AUTS1区；一名日本患者的1585-1587 TTC del(Del312F)和一名高加索患者的G2324A(R558Q)。Del312F位于保守的跨膜区，R558Q位于最后一个跨膜区的远端。此外，在来自五个不同家庭的7名受影响的高加索男子中，发现了一个潜在的与ASD相关的GPR37变异T589M。我们的结果提示GPR37的某些等位基因与ASD的危害有关。GPR37与多巴胺转运体相关，调节多巴胺的摄取，并调节对多巴胺能药物的行为反应。因此，多巴胺能神经元可能参与ASD的发生。然而，我们还在患者未受影响的父亲中检测到Del321F突变，并在受影响的兄弟和未受影响的母亲中检测到R558Q突变。对携带突变等位基因的未受影响的父母的鉴定表明，ASD的表现还受到这些突变以外的因素的影响，包括突变蛋白的内质网压力或性别。我们的研究将为ASD的分子发病机制提供新的视角。
Little is known about the molecular pathogenesis of Autism spectrum disorder (ASD), a neurodevelopmental disorder. Here we identified two mutations in the G-protein-coupled receptor 37 gene (GPR37) localized on chromosome 7q31–33, called the AUTS1 region, of ASD patients; 1585–1587 ttc del (Del312F) in one Japanese patient and G2324A (R558Q) in one Caucasian patient. The Del312F was located in the conserved transmembrane domain, and the R558Q was located in a conserved region just distal to the last transmembrane domain. In addition, a potential ASD-related GPR37 variant, T589M, was found in 7 affected Caucasian men from five different families. Our results suggested that some alleles in GPR37 were related to the deleterious effect of ASD. GPR37 is associated with the dopamine transporter to modulate dopamine uptake, and regulates behavioral responses to dopaminergic drugs. Thus, dopaminergic neurons may be involved in the ASD. However, we also detected the Del321F mutation in the patient's unaffected father and R558Q in not only an affected brother but also an unaffected mother. The identification of unaffected parents that carried the mutated alleles suggested that the manifestation of ASD was also influenced by factors other than these mutations, including endoplasmic reticulum stress of the mutated proteins or gender. Our study will provide the new insight into the molecular pathogenesis of ASD.
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影响因子：
4.4
作者：
Marazziti, D;Golini, E;TocchiniValentini, GP
通讯作者：
TocchiniValentini, GP
影响因子：
30.8
作者：
Durand, Christelle M.;Betancur, Catalina;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
影响因子：
64.8
作者：
Billuart, P;Bienvenu, T;Chelly, J
通讯作者：
Chelly, J
影响因子：
30.8
作者：
D'Adamo, P;Menegon, A;Toniolo, D
通讯作者：
Toniolo, D
影响因子：
9
作者：
通讯作者：
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