Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington.
Am J Med Genet A. 2014 Jun;164A(6):1503-11. doi: 10.1002/ajmg.a.36517. Epub 2014 Apr 3.
The number of single genes associated with neurodevelopmental disorders has increased dramatically over the past decade. The identification of causative genes for these disorders is important to clinical outcome as it allows for accurate assessment of prognosis, genetic counseling, delineation of natural history, inclusion in clinical trials, and in some cases determines therapy. Clinicians face the challenge of correctly identifying neurodevelopmental phenotypes, recognizing syndromes, and prioritizing the best candidate genes for testing. However, there is no central repository of definitions for many phenotypes, leading to errors of diagnosis. Additionally, there is no system of levels of evidence linking genes to phenotypes, making it difficult for clinicians to know which genes are most strongly associated with a given condition. We have developed the Developmental Brain Disorders Database (DBDB: https://www.dbdb.urmc.rochester.edu/home), a publicly available, online-curated repository of genes, phenotypes, and syndromes associated with neurodevelopmental disorders. DBDB contains the first referenced ontology of developmental brain phenotypes, and uses a novel system of levels of evidence for gene-phenotype associations. It is intended to assist clinicians in arriving at the correct diagnosis, select the most appropriate genetic test for that phenotype, and improve the care of patients with developmental brain disorders. For researchers interested in the discovery of novel genes for developmental brain disorders, DBDB provides a well-curated source of important genes against which research sequencing results can be compared. Finally, DBDB allows novel observations about the landscape of the neurogenetics knowledge base.
过去十年中，与神经发育障碍相关的单基因数量显著增加。鉴定这些疾病的致病基因对于临床结果非常重要，因为它可以准确评估预后、遗传咨询、自然病史描述、纳入临床试验，在某些情况下还可以确定治疗方法。临床医生面临着正确识别神经发育表型、识别综合征以及为测试确定最佳候选基因的挑战。然而，许多表型缺乏集中的定义库，导致诊断错误。此外，没有将基因与表型联系起来的证据级别系统，这使得临床医生难以知道哪些基因与特定疾病的关联最强。我们开发了发育性脑障碍数据库 (DBDB：https://www.dbdb.urmc.rochester.edu/home)，这是一个公开的、在线管理的与神经发育障碍相关的基因、表型和综合征的存储库。DBDB 包含了第一个参考发育性脑表型本体论，并且使用了一种新的基因-表型关联证据级别系统。它旨在帮助临床医生做出正确的诊断，为该表型选择最合适的基因检测，并改善发育性脑障碍患者的护理。对于有兴趣发现发育性脑障碍新基因的研究人员，DBDB 提供了一个经过精心管理的重要基因来源，可以将研究测序结果与之进行比较。最后，DBDB 允许对神经遗传学知识库的景观进行新的观察。
