PDF(Pubmed)
Abstract：
3q29 deletion syndrome is caused by a recurrent hemizygous 1.6 Mb deletion on the long arm of chromosome 3. The syndrome is rare (1 in 30,000 individuals) and is associated with mild to moderate intellectual disability, increased risk for autism and anxiety, and a 40-fold increased risk for schizophrenia, along with a host of physical manifestations. However, the disorder is poorly characterized, the range of manifestations is not well described, and the underlying molecular mechanism is not understood. We designed the Emory 3q29 Project to document the range of neurodevelopmental and psychiatric manifestations associated with 3q29 deletion syndrome. We will also create a biobank of samples from our 3q29 deletion carriers for mechanistic studies, which will be a publicly-available resource for qualified investigators. The ultimate goals of our study are three-fold: first, to improve management and treatment of 3q29 deletion syndrome. Second, to uncover the molecular mechanism of the disorder. Third, to enable cross-disorder comparison with other rare genetic syndromes associated with neuropsychiatric phenotypes.
We will ascertain study subjects, age 6 and older, from our existing registry ( 3q29deletion.org ). Participants and their families will travel to Atlanta, GA for phenotypic assessments, with particular emphasis on evaluation of anxiety, cognitive ability, autism symptomatology, and risk for psychosis via prodromal symptoms and syndromes. Evaluations will be performed using standardized instruments. Structural, diffusion, and resting-state functional MRI data will be collected from eligible study participants. We will also collect blood from the 3q29 deletion carrier and participating family members, to be banked at the NIMH Repository and Genomics Resource (NRGR).
The study of 3q29 deletion has the potential to transform our understanding of complex disease. Study of individuals with the deletion may provide insights into long term care and management of the disorder. Our project describes the protocol for a prospective study of the behavioral and clinical phenotype associated with 3q29 deletion syndrome. The paradigm described here could easily be adapted to study additional CNV or single gene disorders with high risk for neuropsychiatric phenotypes, and/or transferred to other study sites, providing a means for data harmonization and cross-disorder analysis.
We will ascertain study subjects, age 6 and older, from our existing registry ( 3q29deletion.org ). Participants and their families will travel to Atlanta, GA for phenotypic assessments, with particular emphasis on evaluation of anxiety, cognitive ability, autism symptomatology, and risk for psychosis via prodromal symptoms and syndromes. Evaluations will be performed using standardized instruments. Structural, diffusion, and resting-state functional MRI data will be collected from eligible study participants. We will also collect blood from the 3q29 deletion carrier and participating family members, to be banked at the NIMH Repository and Genomics Resource (NRGR).
The study of 3q29 deletion has the potential to transform our understanding of complex disease. Study of individuals with the deletion may provide insights into long term care and management of the disorder. Our project describes the protocol for a prospective study of the behavioral and clinical phenotype associated with 3q29 deletion syndrome. The paradigm described here could easily be adapted to study additional CNV or single gene disorders with high risk for neuropsychiatric phenotypes, and/or transferred to other study sites, providing a means for data harmonization and cross-disorder analysis.
摘要：
3q29缺失综合征是由3号染色体长臂上的复发性半合子1.6Mb缺失引起的。该综合征很少见（30,000人中有1人），并且与轻度至中度智力障碍有关，自闭症和焦虑的风险增加，患精神分裂症的风险增加了40倍，伴随着大量的身体表现。然而,这种疾病的特征很差，表现的范围没有很好地描述，和潜在的分子机制是不明白的。我们设计了Emory3q29项目，以记录与3q29缺失综合征相关的神经发育和精神病学表现。我们还将从我们的3q29缺失载体中创建一个生物样本库，用于机理研究，这将是合格调查人员的公开资源。我们研究的最终目标是三个方面：第一，改善3q29缺失综合征的管理和治疗。第二,揭示疾病的分子机制.第三，与其他与神经精神表型相关的罕见遗传综合征进行交叉障碍比较。
我们将确定研究对象，6岁及以上，从我们现有的注册表（3q29deletion.org）。参与者和他们的家人将前往亚特兰大，用于表型评估的GA，特别强调对焦虑的评估，认知能力,自闭症症状学，以及通过前驱症状和综合症患上精神病的风险。评价将使用标准化仪器进行。结构,扩散,静息态功能MRI数据将从符合条件的研究参与者中收集.我们还将从3q29删除载体和参与的家庭成员中收集血液，将存入NIMH存储库和基因组学资源(NRGR)。
3q29缺失的研究有可能改变我们对复杂疾病的理解。对缺失个体的研究可以提供对该疾病的长期护理和管理的见解。我们的项目描述了与3q29缺失综合征相关的行为和临床表型的前瞻性研究方案。这里描述的范例可以很容易地适应研究其他CNV或单基因疾病，这些疾病具有神经精神表型的高风险。和/或转移到其他研究地点，为数据协调和交叉障碍分析提供了一种手段。
我们将确定研究对象，6岁及以上，从我们现有的注册表（3q29deletion.org）。参与者和他们的家人将前往亚特兰大，用于表型评估的GA，特别强调对焦虑的评估，认知能力,自闭症症状学，以及通过前驱症状和综合症患上精神病的风险。评价将使用标准化仪器进行。结构,扩散,静息态功能MRI数据将从符合条件的研究参与者中收集.我们还将从3q29删除载体和参与的家庭成员中收集血液，将存入NIMH存储库和基因组学资源(NRGR)。
3q29缺失的研究有可能改变我们对复杂疾病的理解。对缺失个体的研究可以提供对该疾病的长期护理和管理的见解。我们的项目描述了与3q29缺失综合征相关的行为和临床表型的前瞻性研究方案。这里描述的范例可以很容易地适应研究其他CNV或单基因疾病，这些疾病具有神经精神表型的高风险。和/或转移到其他研究地点，为数据协调和交叉障碍分析提供了一种手段。
