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：脑白质营养不良是一组异质性复杂的神经系统疾病，影响髓磷脂或白质的发生和维持。下一代测序和新兴基因组技术提高了识别疾病分子原因的能力，使得疾病过程和针对性治疗的改进特征。然而，分子脑白质营养不良的表征需要专家的监督，就像当前的基因疾病一样验证和临床可操作性尚未得到正式表征。当前诊断测试包括生化和基因检测，但只有 50-80% 的患者能够确诊通过脑部磁共振成像检查发现髓鞘质紊乱。这让许多患者诊断不确定，这可能会限制治疗选择，导致情绪困扰，并限制获得治疗的机会临床试验，对于一些家庭来说，还有生殖选择。全球脑白质营养不良倡议 (GLIA) 是一个由罕见疾病临床研究网络资助的科学家和倡导者联盟他们共同努力推进脑白质营养不良的研究和临床试验。 GLIA 联盟已与 ClinGen 接洽，利用我们的技术建立基因和变异管理专家小组特定疾病的专家和生物信息学家来策划和评估脑白质营养不良相关基因和变体。目前至少有 240 个基因属于该组的范围，这些基因将被由该小组精心策划和管理。对于 25 个最常诊断的基因，脑白质营养不良，该小组将提供全面的变异治疗，包括临床上最可操作的致病变异。该应用程序的总体影响将是澄清脑白质营养不良中的疾病与基因关联，提高对脑白质营养不良临床可操作性的理解这些疾病，并阐明关键高频基因变异的致病性。在一起，这些活动将为脑白质营养不良社区提供新生儿筛查的明确诊断，临床试验和临床护理。