Kline Antonie D, Krantz Ian D, Bando Masashige, Shirahige Katsuhiko, Chea Stephenson, Sakata Toyonori, Rao Suhas, Dorsett Dale, Singh Vijay Pratap, Gerton Jennifer L, Horsfield Julia A, Calof Anne L, Katz Olivia, Grados Marco, Raible Sarah, Barañano Kristin, Lyon Gholson, Musio Antonio, Carrico Cheri S, Clemens Douglas K, Caudill Patti, Massa Valentina, McGill Bryan E, Dommestrup Aila, O'Connor Julia, Haaland Richard E
Department of Pediatrics, Greater Baltimore Medical Center, Harvey Institute for Human Genetics, Baltimore, Maryland.
Division of Human Genetics, The Children's Hospital of Philadelphia.
Am J Med Genet A. 2019 Jun;179(6):1080-1090. doi: 10.1002/ajmg.a.61108. Epub 2019 Mar 15.
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 , 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.
科妮莉亚·德朗格综合征（CdLS）是由于黏连蛋白复合体基因发生突变所致，被描述为一种转录调控紊乱疾病。在这个不断发展的领域中，其表型包括身材矮小、小头畸形、智力障碍、面部特征多样以及器官受累，导致临床表现相互重叠，既有已确定的综合征，也有新描述的病症。所有形式的CdLS患者都有多种并发症，包括神经发育、喂养、颅面和沟通方面的问题。现在人们对CdLS中应对机制和挑战性行为的管理、正常行为的破坏以及行为如何塑造个体在家庭中的生活有了更好的理解。已知一些精神药物对行为有效。其他药物，例如消炎痛，正在研究其对基因表达、胎儿脑组织、小鼠脑形态和功能以及含有CdLS相关突变的人类成纤维细胞的影响。发育研究已经阐明了心脏缺陷的起源以及胎盘在CdLS中的作用。染色体结构和黏连蛋白复合体结构得以阐明，从而对调控方面和控制有了更好的理解。例如，当存在突变时，黏连蛋白形成环结构域以促进增强子 - 启动子相互作用的过程可能会被消除，并且在胚胎学上，受精卵的核结构会被破坏。现在已知有几个重要基因与黏连蛋白相互作用，包括Brca2。以下摘要来自于2018年6月在明尼苏达州明尼阿波利斯举行的第8届科妮莉亚·德朗格综合征科学与教育研讨会（在CdLS基金会全国会议之前），由马里兰州巴尔的摩的GBMC提供AMA CME学分。所有研究均已获得伦理委员会批准。
