Clinical and Molecular Characterization of Familial Marrow Failure Syndrome

描述（由申请人提供）：遗传性骨髓衰竭综合征（IBMFS）是一组异质性疾病，其特征为骨髓衰竭、先天性异常和骨髓增生异常综合征（MDS）易感性。迄今为止，IBMFS的研究主要集中在儿科患者，但这些研究在出现血细胞减少的成人中越来越多地得到认可。目前还没有定义IBMFS成人患者最佳护理的范例。一个重要的患者子集不属于已知的IBMFS类别。IBMFS患者的诊断和医疗护理受到我们对遗传原因缺乏了解的限制。我们将在儿科/成人诊所和实验室之间进行互补的双向研究，以调查IBMFS的临床特征，遗传病因学和病理生理学。我们还将利用最新的技术进步作为平台，为这些综合征开发新的诊断测试。鉴定有助于骨髓衰竭的分子途径应该提供对调节造血的全球分子途径的见解，并告知我们对一般人群中获得性骨髓衰竭和MDS的理解。 公共卫生相关性：了解导致骨髓衰竭的遗传途径将有助于开发新的诊断测试和合理设计的医学疗法。阐明遗传性骨髓衰竭的分子机制，将提供骨髓衰竭在一般人群中出现的见解。

DESCRIPTION (provided by applicant): The inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of disorders characterized by marrow failure, congenital anomalies, and predisposition to myelodysplastic syndromes (MDS). Studies of IBMFS to date have largely focused on pediatric patients, but these are increasingly recognized in adults presenting with cytopenia(s). There are no paradigms defining the optimal care of adult patients with IBMFS. A significant subset of patients fail to fall within the known categories of IBMFS. The diagnosis and medical care of IBMFS patients are limited by our lack of knowledge regarding genetic causes. We will pursue complementary bidirectional studies moving between the pediatric/adult clinics and the laboratory to investigate the clinical features, genetic etiology, and pathophysiology of IBMFS. We will also exploit recent technological advances as a platform to develop novel diagnostic tests for these syndromes. The identification of molecular pathways contributing to marrow failure should provide insights into global molecular pathways regulating hematopoiesis as well as inform our understanding of acquired marrow failure and MDS in the general population. PUBLIC HEALTH RELEVANCE: Understanding the genetic pathways contributing to marrow failure will allow the development of new diagnostic tests and rationally designed medical therapies. Elucidating the molecular mechanisms underlying inherited marrow failure will provide insights into marrow failure arising in the general population.