Gene Curation Expert Panel for Syndromic Disorders

综合症疾病基因管理专家小组

基本信息

批准号：
10685357
负责人：
Anne O'Donnell-Luria
金额：
$ 37.82万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-17 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10685357
关键词：
Aloral Australia Caring Case Series Case Study Child Childhood Classification ClinVar Clinical Clinical Management Communities Complex Data Dedications Diagnostic Diagnostic tests Disease England Family Planning Funding Genes Genetic Genomics Human Resources Infant Institution International Laboratories Level of Evidence Medical Molecular Diagnosis Molecular Diagnostic Testing Morbidity - disease rate Nature Online Mendelian Inheritance In Man Ontology Organ Pathogenicity Pathway interactions Pattern Phenotype Population Positioning Attribute Pregnancy Processed Genes Productivity Publications Publishing Rare Diseases Recurrence Registries Reporting Research Research Personnel Risk Schedule Singapore Structural Congenital Anomalies Syndrome Testing United States National Institutes of Health Variant care delivery clinical care clinical diagnosis clinical diagnostics clinical practice congenital anomaly exome sequencing expedited review experience falls genetic counselor genetic disorder diagnosis genetic testing genome resource genome sequencing improved infant death interest knowledgebase meetings member model organism mortality next generation sequencing novel rare condition rare genetic disorder research clinical testing research study working group

项目摘要

ABSTRACT Syndromic disorders account for a large proportion of the rare genetic disorders that impact the pediatric population, including many conditions with structural birth defects and other congenital anomalies. These conditions are a disproportionate cause of morbidity and mortality. Accurate molecular diagnosis is important for medical management, family planning, and engagement in research studies. Next generation sequencing has driven the pace of discovery of novel genetic syndromes, yet there are marked inconsistencies in the level of evidence for gene-disease relationships (GDRs) that complicate the application of genetic testing. We have formed the Syndromic Disorders Gene Curation Expert Panel (SD-GCEP), an international group of disease experts, gene curation framework experts, and biocurators representing 23 institutions across 5 continents to thoroughly curate the evidence supporting the relationship of a gene in causing a disease, and to quantify the strength of that evidence using the framework developed by the Clinical Genome Resource (ClinGen). The SD- GCEP consists of representatives from major stakeholders including Online Mendelian Inheritance in Man (OMIM), Monarch Initiative’s Mondo disease ontology, Genomics England PanelApp, PanelApp Australia, Centers for Mendelian Genomics, diagnostic laboratories (Ambry, Illumina, Invitae), practicing clinical geneticists, genetic counselors, and rare disease and model organism researchers. In Aim 1, we will perform 68 GDR precurations, curations and recurations representing the most commonly tested syndromic disorders not within the purview of other GCEPs, which generally focus on a specific organ or pathway. In Aim 2, we will perform 89 precurations, curations, and recurations for syndromic GDRs identified through clinical exome and genome sequencing performed by diagnostic laboratories with personnel involved in the SD-GCEP. In Aim 3A, we will perform 24 precurations, curations, and recurations for newly discovered syndromic GDRs from the Centers for Mendelian Genomics, as these are of high interest to diagnostic laboratories to determine when genes should be added to panels and to clinicians to guide clinical diagnosis and management. The SD-GCEP is highly experienced and collaborative. In Aim 3B, we will continue to accept requests from other GCEPs to curate 15 GDRs of interest that are beyond the scope of the other GCEP due to the syndromic nature of the condition. In total, we will perform 196 precurations, curations, and recurations of GDRs for syndromic disorders over three years. All curations will be performed using the ClinGen Gene Curation Interface and publicly shared though the ClinGen knowledgebase to improve genetic testing and diagnosis for syndromic disorders and to highlight where further research is needed.

抽象的在影响儿科的罕见遗传性疾病中，综合征性疾病占很大比例人口，包括许多患有结构性出生缺陷和其他先天异常的情况。疾病是发病率和死亡率的一个不成比例的原因，准确的分子诊断对于。医疗管理、计划生育和参与下一代测序。推动了新的遗传综合症的发现步伐，但在水平上存在明显的不一致我们拥有使基因检测的应用变得复杂的基因与疾病关系（GDR）的证据。成立了综合征性疾病基因治疗专家组 (SD-GCEP)，这是一个国际疾病组代表五大洲 23 个机构的专家、基因策展框架专家和生物策展人彻底整理支持基因与导致疾病的关系的证据，并量化使用临床基因组资源 (ClinGen) 开发的框架来验证该证据的强度。 GCEP 由来自主要利益相关者的代表组成，包括在线人类孟德尔遗传 (OMIM)、Monarch Initiative 的 Mondo 疾病本体论、Genomics England PanelApp、PanelApp Australia、孟德尔基因组学中心、诊断实验室（Ambry、Illumina、Invitae）、临床实践遗传学家、遗传咨询师以及罕见疾病和模式生物研究人员在目标 1 中，我们将执行 68 项任务。 GDR precurations、curations 和 recurations 代表最常测试的综合征疾病，但不在其他 GCEP 的范围内，这些 GCEP 通常关注特定的器官或途径。在目标 2 中，我们将。针对通过临床外显子组识别的综合征 GDR 进行 89 项预治疗、治疗和再治疗在 Aim 3A 中，由诊断实验室与参与 SD-GCEP 的人员进行基因组测序。我们将对新发现的 GDR 综合征进行 24 次预治疗、治疗和再治疗孟德尔基因组学中心，因为诊断实验室对这些中心非常感兴趣，以确定何时应将基因添加到组中并首先指导 SD-GCEP。在 Aim 3B 中，我们将继续接受其他 GCEP 的请求，以实现目标。策划 15 个感兴趣的 GDR，由于其综合征性质，这些 GDR 超出了其他 GCEP 的范围总共，我们将针对综合征疾病进行 196 次 GDR 治疗、治疗和再治疗。三年内的所有策展都将使用 ClinGen 基因策展界面进行并公开共享。通过 ClinGen 知识库来改进综合征疾病的基因检测和诊断，并强调需要进一步研究的地方。