单基因疾病占神经发育障碍人群归因风险的很大比例。然而,通常缺乏推断给定遗传变异与特定神经发育障碍之间因果关系所需的数据。认识到这一科学障碍,13个智力和发育障碍研究中心(IDDRC)成立了一个联盟,以创建大脑基因登记处(BGR)。存储库将临床遗传数据与来自具有推定脑基因变异的参与者的表型数据配对.表型图谱由电子健康记录(EHR)和一系列远程管理的标准化评估组成,统称为快速神经行为评估协议(RNAP)。其中包括认知,神经学,和神经精神病学评估,以及对注意力缺陷多动障碍(ADHD)和自闭症谱系障碍(ASD)的评估。BGR参与者在临床基因组资源(ClinGen)GenomeConnect中的共同注册可以在ClinVar中显示变异信息。BGR目前包含479名参与者的数据,其中55%是男性,6%亚洲人,6%黑人或非裔美国人,76%白色,和12%的西班牙裔/拉丁裔。BGR中有超过200个基因,有12个或更多的参与者在这些基因中都有变异:CACNA1A,DNMT3A,SLC6A1、SETD5和MYT1L。超过30%的变体是从头的,并且43%被分类为具有不确定显著性的变体(VUS)。认知或发育筛选的平均标准分数低于BGR队列的平均值。EHR数据显示发育迟缓是该样本中最早和最常见的诊断,其次是言语和语言障碍,ASD,和ADHD。BGR数据已用于加速ClinGen的BGR智力障碍(ID)-自闭症(ASD)基因固化专家小组评估的36个基因的基因疾病有效性。总之,BGR是有兴趣推进脑基因转化研究的利益相关者使用的资源,并继续招募具有临床报道变异的参与者,以建立丰富且特征明确的国家资源,以促进神经发育障碍的研究。
Monogenic disorders account for a large proportion of population-attributable risk for neurodevelopmental disabilities. However, the data necessary to infer a causal relationship between a given genetic variant and a particular neurodevelopmental disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual and Developmental Disabilities Research Centers (IDDRCs) formed a consortium to create the Brain Gene Registry (BGR), a repository pairing clinical genetic data with phenotypic data from participants with variants in putative brain genes. Phenotypic profiles are assembled from the electronic health record (EHR) and a battery of remotely administered standardized assessments collectively referred to as the Rapid Neurobehavioral Assessment Protocol (RNAP), which include cognitive, neurologic, and neuropsychiatric assessments, as well as assessments for attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Co-enrollment of BGR participants in the Clinical Genome Resource\'s (ClinGen\'s) GenomeConnect enables display of variant information in ClinVar. The BGR currently contains data on 479 participants who are 55% male, 6% Asian, 6% Black or African American, 76% white, and 12% Hispanic/Latine. Over 200 genes are represented in the BGR, with 12 or more participants harboring variants in each of these genes: CACNA1A, DNMT3A, SLC6A1, SETD5, and MYT1L. More than 30% of variants are de novo and 43% are classified as variants of uncertain significance (VUSs). Mean standard scores on cognitive or developmental screens are below average for the BGR cohort. EHR data reveal developmental delay as the earliest and most common diagnosis in this sample, followed by speech and language disorders, ASD, and ADHD. BGR data has already been used to accelerate gene-disease validity curation of 36 genes evaluated by ClinGen\'s BGR Intellectual Disability (ID)-Autism (ASD) Gene Curation Expert Panel. In summary, the BGR is a resource for use by stakeholders interested in advancing translational research for brain genes and continues to recruit participants with clinically reported variants to establish a rich and well-characterized national resource to promote research on neurodevelopmental disorders.