Rare lung diseases in children: phenotyping, genetics, course and disease burden

儿童罕见肺部疾病：表型、遗传学、病程和疾病负担

• 批准号: 413551332
• 负责人: Professor Dr. Matthias Griese
• 金额: --
• 依托单位: Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/413551332?language=en
• 关键词: Rare; lung; diseases; children; phenotyping

Childhood interstitial lung diseases (chILD) comprises many, rare chronic diseases, often caused by strong genetic factors, whose disease course is largely unexplored. The Children's Lung Registry with Biobank (chILD-EU) is an open platform for the collection, peer-review, and monitoring of these diseases. In the previous funding period, we implemented and successfully applied pathways for data-based, molecular genetics, functional and clinical characterization of chILD, and also generated new, testable hypotheses. These will now be answered in carefully phenotyped patient populations with the required biomaterials, by applying appropriate, technically advanced molecular methods. The 1st work package will investigate whether the proportion of etiologically resolved cases of chILD can be increased by at least 10% by targeted use of advanced genomic and transcriptome analyses. The 2nd work package will use a large cohort of families with persistent tachypnea of infancy (NEHI) to investigate the hypothesis of whether etiologically relevant genes are located in the candidate regions we have identified on chromosome 1. In the 3rd work package, we will investigate whether pulmonary fibrosis in children adversely affects long-term outcome, whether secondary pulmonary hypertension has no effect, and whether infants with chILD and extrapulmonary organ manifestations have increased morbidity and poorer quality of life.We expect to molecularly elucidate new disease entities, improve their genetic diagnosis, and clarify the impact of childhood pulmonary fibrosis, pulmonary hypertension, and the influence of co-morbidities on the long-term course of patients with childhood interstitial lung diseases.

儿童间质性肺病（child）包括许多罕见的慢性疾病，通常由强遗传因素引起，其病程基本上未被探索。儿童肺部登记与生物库（child-EU）是一个开放的平台，用于收集，同行评议和监测这些疾病。在上一个资助期，我们实施并成功应用了基于数据的途径，分子遗传学，儿童功能和临床表征，并产生了新的，可检验的假设。这些问题现在将通过应用适当的、技术先进的分子方法，在具有所需生物材料的仔细分型的患者群体中得到回答。第一个工作包将研究通过有针对性地使用先进的基因组和转录组分析，是否可以将病因学解决的儿童ILD病例的比例增加至少10%。第二个工作包将使用一个大的婴儿期持续性呼吸急促（NEHI）家庭队列来研究病因相关基因是否位于我们在1号染色体上确定的候选区域的假设。在第三个工作包中，我们将研究儿童肺纤维化是否对长期结局产生不利影响，继发性肺动脉高压是否没有影响，以及有儿童和肺外器官表现的婴儿是否会增加发病率和降低生活质量。我们期望从分子水平上阐明新的疾病实体，改善其遗传诊断，并阐明儿童肺纤维化、肺动脉高压、以及共病对儿童间质性肺病患者长期病程的影响。