GLIA-CTN Genomic Expert Curation Panel

GLIA-CTN 基因组专家管理小组

基本信息

批准号：
10630404
负责人：
Adeline Lucie Vanderver
金额：
$ 41.76万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-15 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10630404
关键词：
Advocacy Advocate Affect Axon Biochemical Bioinformatics Brain Diseases Central Nervous System Childhood Classification ClinVar Clinical Research Clinical Trials Communities Complex Diagnosis Diagnostic Diagnostic tests Disease Disputes Documentation Enrollment Etiology Family Funding Future Gene Frequency Genes Genetic Genomics Goals Grant Guidelines Hereditary Disease Knowledge Laboratories Lead Leadership Literature Maintenance Modification Molecular Morbidity - disease rate Myelin Natural History Neonatal Screening Neurologic Outcome Pathogenicity Patients Positioning Attribute Procedures Process Publications Rare Diseases Recommendation Research Personnel Resources Role Scientist Standardization Structure System Technology Testing Therapeutic Training Validation Variant Work accurate diagnosis brain magnetic resonance imaging clinical care clinical decision-making clinical trial readiness clinically actionable diagnostic panel diagnostic tool emotional distress falls genetic counselor genetic testing genetic variant improved leukodystrophy member mortality next generation sequencing optimism reproductive response white matter

项目摘要

Abstract: Leukodystrophies are a heterogeneous group of complex neurological conditions impacting the genesis and maintenance of myelin, or white matter. Next generation sequencing and emerging genomic technologies have improved the ability to identify molecular causes of disease, allowing for the improved characterization of disease processes and focused therapeutics. However, molecular characterization of leukodystrophies requires expert oversight as much of the current gene-disease validation and clinical actionability have not been formally characterized. Current diagnostic testing includes biochemical and genetic testing but reveals a diagnosis in only 50-80% of patients said to have a myelin disorder by brain magnetic resonance imaging. This leaves many patients with an uncertain diagnosis, which can limit treatment options, cause emotional distress, and limit access to clinical trials and, for some families, reproductive choices. The Global Leukodystrophy Initiative (GLIA) is a Rare Disease Clinical Research Network funded consortium of scientists and advocates that work collaboratively to advance the study of and clinical trials for leukodystrophies. The GLIA consortium has approached ClinGen to establish Gene and Variant Curation Expert Panels, using our disease-specific experts and bioinformaticians to curate and assess leukodystrophy-related genes and variants. There are at least 240 genes that currently fall in the purview of this group, which will be expertly curated and managed by this group. For the 25 most commonly diagnosed genes causing leukodystrophy, this group will provide comprehensive variant curation, including the most clinically actionable disease-causing variants. The overall impact of this application will be to clarify the disease-gene association in the leukodystrophies, improve understanding of clinical actionability in these disorders, and clarify the pathogenicity of variants in key high frequency genes. Together, these activities will provide the leukodystrophy community with diagnostic clarity for newborn screening, clinical trials and clinical care.

抽象的：白细胞营养不良是一组复杂的神经系统疾病的异构群体，影响了髓磷脂或白质的起源和维护。下一代测序和新兴基因组技术提高了鉴定疾病分子原因的能力，从而使疾病过程和重点治疗的表征改进。但是，分子白细胞营养不良的表征需要专家监督，这是当前基因疾病的大部分验证和临床可行性尚未正式表征。当前的诊断测试包括生化和基因检测，但显示仅50-80％的患者诊断通过大脑磁共振成像具有髓磷脂障碍。这使许多患者患有不确定的诊断，可以限制治疗方案，造成情绪困扰，并限制进入临床试验，对于某些家庭而言，是生殖选择。全球白细胞营养不良倡议（GLIA）是罕见的疾病临床研究网络，由科学家和拥护者的财团资助该协作努力促进对白细胞营养不良的研究和临床试验。神经胶质财团已接近Clingen，使用我们的疾病特异性专家和生物信息学家策划和评估白细胞营养不良相关的基因和变体。目前至少有240个基因属于该组的权限，这将是由这个小组熟练策划和管理。对于25个最常见的基因引起的白细胞营养不良，该组将提供全面的变体策划，包括临床上最多的策划可操作的致病变体。该应用程序的总体影响是澄清白细胞病中的疾病基因关联，提高对临床可行性的理解这些疾病，并阐明关键高频基因中变体的致病性。在一起，这些活动将为白细胞增多症社区提供新生儿筛查的诊断清晰度，临床试验和临床护理。