García-Recio Adrián, Santos-Gómez Ana, Soto David, Julia-Palacios Natalia, García-Cazorla Àngels, Altafaj Xavier, Olivella Mireia
Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Hum Mutat. 2021 Jan;42(1):8-18. doi: 10.1002/humu.24141. Epub 2020 Nov 30.
Glutamatergic neurotransmission is crucial for brain development, wiring neuronal function, and synaptic plasticity mechanisms. Recent genetic studies showed the existence of autosomal dominant de novo GRIN gene variants associated with GRIN-related disorders (GRDs), a rare pediatric neurological disorder caused by N-methyl- d-aspartate receptor (NMDAR) dysfunction. Notwithstanding, GRIN variants identification is exponentially growing and their clinical, genetic, and functional annotations remain highly fragmented, representing a bottleneck in GRD patient's stratification. To shorten the gap between GRIN variant identification and patient stratification, we present the GRIN database (GRINdb), a publicly available, nonredundant, updated, and curated database gathering all available genetic, functional, and clinical data from more than 4000 GRIN variants. The manually curated GRINdb outputs on a web server, allowing query and retrieval of reported GRIN variants, and thus representing a fast and reliable bioinformatics resource for molecular clinical advice. Furthermore, the comprehensive mapping of GRIN variants' genetic and clinical information along NMDAR structure revealed important differences in GRIN variants' pathogenicity and clinical phenotypes, shedding light on GRIN-specific fingerprints. Overall, the GRINdb and web server is a resource for molecular stratification of GRIN variants, delivering clinical and investigational insights into GRDs. GRINdb is accessible at http://lmc.uab.es/grindb.
谷氨酸能神经传递对于大脑发育、神经元功能连接以及突触可塑性机制至关重要。最近的遗传学研究表明，存在与GRIN相关疾病（GRD）相关的常染色体显性新生GRIN基因变异，GRD是一种由N-甲基-D-天冬氨酸受体（NMDAR）功能障碍引起的罕见儿童神经系统疾病。尽管如此，GRIN变异的识别呈指数级增长，其临床、遗传和功能注释仍然高度分散，这是GRD患者分层的一个瓶颈。为了缩短GRIN变异识别与患者分层之间的差距，我们推出了GRIN数据库（GRINdb），这是一个公开可用、无冗余、更新且经过整理的数据库，收集了来自4000多个GRIN变异的所有可用遗传、功能和临床数据。经过人工整理的GRINdb在网络服务器上输出，允许查询和检索已报道的GRIN变异，因此是一种用于分子临床建议的快速可靠的生物信息学资源。此外，沿着NMDAR结构对GRIN变异的遗传和临床信息进行的全面映射揭示了GRIN变异在致病性和临床表型方面的重要差异，为GRIN特异性特征提供了线索。总体而言，GRINdb和网络服务器是GRIN变异分子分层的资源，为GRD提供临床和研究见解。可通过http://lmc.uab.es/grindb访问GRINdb。
