PDF(Pubmed)
Abstract：
Cornelia de Lange Syndrome (CdLS), due to mutations in genes of the cohesin protein complex, is described as a disorder of transcriptional regulation. Phenotypes in this expanding field include short stature, microcephaly, intellectual disability, variable facial features and organ involvement, resulting in overlapping presentations, including established syndromes and newly described conditions. Individuals with all forms of CdLS have multifaceted complications, including neurodevelopmental, feeding, craniofacial, and communication. Coping mechanisms and management of challenging behaviors in CdLS, disruption of normal behaviors, and how behavior molds the life of the individual within the family is now better understood. Some psychotropic medications are known to be effective for behavior. Other medications, for example, Indomethacin, are being investigated for effects on gene expression, fetal brain tissue, brain morphology and function in Drosophila, mice, and human fibroblasts containing CdLS-related mutations. Developmental studies have clarified the origin of cardiac defects and role of placenta in CdLS. Chromosome architecture and cohesin complex structure are elucidated, leading to a better understanding of regulatory aspects and controls. As examples, when mutations are present, the formation of loop domains by cohesin, facilitating enhancer-promotor interactions, can be eliminated, and embryologically, the nuclear structure of zygotes is disrupted. Several important genes are now known to interact with cohesin, including Brca2. The following abstracts are from the 8th Cornelia de Lange Syndrome Scientific and Educational Symposium, held in June 2018, Minneapolis, MN, before the CdLS Foundation National Meeting, AMA CME credits provided by GBMC, Baltimore, MD. All studies have been approved by an ethics committee.
摘要：
CorneliadeLange综合征（CdLS），由于粘附蛋白复合物的基因突变，被描述为转录调控障碍。这个扩展领域的表型包括身材矮小，小头畸形,智力残疾,可变的面部特征和器官受累，导致重叠的演示，包括既定的综合症和新描述的条件。患有各种形式的CdLS的个体都有多方面的并发症，包括神经发育,喂养,颅面,和沟通。CdLS中挑战性行为的应对机制和管理，破坏正常行为，以及行为如何塑造家庭中个人的生活现在得到了更好的理解。已知一些精神药物对行为有效。其他药物,例如,吲哚美辛,正在研究对基因表达的影响，胎儿脑组织,果蝇的大脑形态和功能，老鼠,和含有CdLS相关突变的人成纤维细胞。发育研究已经阐明了心脏缺陷的起源和胎盘在CdLS中的作用。阐明了染色体结构和粘附蛋白复杂结构，从而更好地理解监管方面和控制。作为例子,当突变存在时，环域的形成，促进增强子-启动子相互作用，可以消除，和胚胎学，受精卵的核结构被破坏。现在已知几个重要的基因与粘附蛋白相互作用，包括Brca2.以下摘要来自第八届CorneliadeLange综合征科学和教育研讨会，2018年6月，明尼阿波利斯，MN,在CdLS基金会全国会议之前，由GBMC提供的AMACME学分，巴尔的摩,MD.所有研究均已获得伦理委员会的批准。
