Neuroimaging of the schizophrenia-associated 3q29 deletion

总结 3q 29缺失综合征是由一种典型的复发性1.6 Mb杂合性缺失引起的 并与一系列神经精神表型相关，包括轻度至中度 智力障碍，自闭症，焦虑，精神分裂症的风险增加40倍。虽然 3q 29缺失是罕见的（约1/30，000出生），其神经精神表型的高风险， 其相对较低的复杂性（22个基因在缺失区间）表明， 可能会屈服于审问研究的分子，细胞，和行为的后果， 在人类患者和模型系统中，我们的团队和其他人正在进行删除。 然而，大脑结构和功能的紊乱还没有得到阐明，我们建议 使用结构、弥散和静息态功能性MRI对其进行研究。这是第一 3q 29缺失的神经影像学研究。为了实现我们的目标，我们建立了 埃默里3q 29项目（http：//genome.emory.edu/3q29/），其总体目标是 了解3q 29缺失相关表型的基础。我们还创建了3Q 29 删除登记处（3q29deletion.org），尽管删除的人口频率较低， （1/30，000）我们已经确定了100多名携带者（年龄从1.5 - 34岁不等）， 有史以来最大的一批这个基础设施，沿着我们现有的国立卫生研究院资助的赠款 （“模拟精神分裂症相关3q 29缺失的人类神经元表型”，MPI Mulle/Bassell，1 R 01 MH 110701），使我们能够进行面对面的表型评估， 3q 29缺失患者，产生了丰富的行为和临床数据集。现有的努力， 虽然令人兴奋，但缺乏大脑系统层面的综合数据收集。我们建议增加 这是我们正在进行的数据收集工作的一个额外方面， 结构连接和功能连接改变是3q 29的特征 缺失综合征我们还将进行3q 29缺失和另一种变体之间的比较 患精神分裂症的风险极高，即众所周知的22q11.2缺失。定义 3q 29缺失对脑系统的影响可能是一个基本的连接桥梁分子， 缺陷和行为表现。

SUMMARY 3q29 deletion syndrome is caused by a recurrent typically de novo 1.6 Mb heterozygous deletion and is associated with a range of neuropsychiatric phenotypes, including mild to moderate intellectual disability, autism, anxiety, and a 40-fold increased risk for schizophrenia. Although the 3q29 deletion is rare (~1 in 30,000 births), its high risk for neuropsychiatric phenotypes coupled with its relatively low complexity (22 genes in the deletion interval) suggest the pathophysiology may yield to interrogation. Studies of the molecular, cellular, and behavioral consequences of the deletion, in both human patients and model systems, are underway by our group and others. However, disturbances in brain structure and function are not yet articulated, and we propose to investigate them using structural, diffusion, and resting-state functional MRI. This is the first neuroimaging study of the 3q29 deletion. To accomplish our aims, we have established the Emory 3q29 Project (http://genome.emory.edu/3q29/), where the overarching goal is to understand the basis of 3q29 deletion-associated phenotypes. We have also created the 3q29 deletion registry (3q29deletion.org), where despite the low population frequency of the deletion (1 in 30,000) we have ascertained over 100 carriers (ranging in age from 1.5 – 34 years), the largest cohort ever assembled. This infrastructure, along with our existing NIH-funded grant (“Modeling the Human Neuronal Phenotype of the Schizophrenia-Associated 3q29 Deletion,” MPI Mulle/Bassell, 1 R01 MH110701), allows us to conduct in-person phenotypic assessments of 3q29 deletion patients, generating a rich set of behavioral and clinical data. This existing effort, while exciting, lacks integrated collection of data at the level of brain systems. We propose adding this additional dimension of data collection to our ongoing effort in order to identify volumetric, structural connectivity, and functional connectivity alterations that are characteristic of 3q29 deletion syndrome. We will also perform a comparison between 3q29 deletion and another variant with an extremely high risk for schizophrenia, the well-known 22q11.2 deletion. Defining the impact of the 3q29 deletion on brain systems may serve as a fundamental link bridging molecular deficits and behavioral manifestations.