GLIA-CTN Genomic Expert Curation Panel

GLIA-CTN 基因组专家管理小组

• 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
• 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

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.

摘要： 脑白质营养不良是一组复杂的神经疾病，影响脑白质营养不良 髓鞘或白质的发生和维持。下一代测序和新兴 基因组技术已经提高了识别疾病分子原因的能力，允许 改进了疾病过程的特征和重点治疗方法。然而，分子 脑白质营养不良的特征需要专家监督，就像目前的许多基因疾病一样 有效性和临床可操作性尚未正式确定。当前诊断测试 包括生化和基因检测，但只有50%-80%的患者被诊断为 脑部核磁共振成像显示有髓鞘紊乱。这让许多患者患上了 不确定的诊断，这可能会限制治疗选择，导致情绪困扰，并限制获得 临床试验，对一些家庭来说，还有生育选择。全球脑白质营养不良倡议 (GILA)是一个由科学家和倡导者组成的罕见疾病临床研究网络资助的联盟 这些合作推动了脑白质营养不良的研究和临床试验。神经胶质细胞 财团已与Clingen接洽，以建立基因和变体修复专家小组，使用我们的 疾病特异性专家和生物信息学家，以管理和评估脑白质营养不良相关基因 还有变种。目前至少有240个基因属于这个小组的范围，这将是 由该组织精心策划和管理。关于25种最常见的导致疾病的基因 脑白质营养不良，这一组将提供全面的变异治疗，包括最临床的 可操作的致病变种。这个应用程序的总体影响将是澄清 脑白质营养不良的疾病-基因关联，提高对临床可操作性的理解 这些疾病，并阐明了关键高频基因变异的致病性。加在一起，这些 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。