Clinical and Molecular Characterization of Familial Marrow Failure Syndrome

家族性骨髓衰竭综合征的临床和分子特征

• 批准号: 8214798
• 负责人: Janis L Abkowitz
• 金额: $ 49.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8214798
• 关键词: Adult; Biogenesis; Bioinformatics; Biological Assay; Blood; Caring; Categories; Child; Childhood; Clinic; Clinical; Clonal Evolution; Collaborations; Development; Diagnosis; Diagnostic tests; Disease; Disease Progression; Dysmyelopoietic Syndromes; Erythropoiesis; Failure; Family; Family member; Fertility; Functional disorder; Future; Gene Chips; General Population; Genetic; Genetic Predisposition to Disease; Genomic Instability; Genomics; Goals; Hematopoiesis; Hematopoietic stem cells; Inherited; Interdisciplinary Study; Knowledge; Laboratories; Link; Marrow; Medical; Molecular; Mutation; Myelogenous; Pancytopenia; Pathway interactions; Patient Care; Patients; Predisposition; Rare Diseases; Research; Resources; Sampling; Syndrome; System; Time; Work; clinical care; clinical phenotype; cost effective; cytopenia; design; exome; falls; genome sequencing; improved; innovation; insight; kindred; new technology; next generation; novel diagnostics; programs; repository

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.

描述（由申请人提供）：遗传的骨髓衰竭综合征（IBMF）是一组异质性疾病，其特征是骨髓衰竭，先天性异常和对骨髓增生综合征（MDS）的倾向。迄今为止，对IBMF的研究主要集中在小儿患者上，但是这些患者越来越多地在患有细胞质症的成年人中得到认可。没有定义IBMF患者最佳护理的范例。大量患者未能属于已知类别的IBMF。 IBMFS患者的诊断和医疗保健受到我们对遗传原因的知识的限制。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，以研究IBMF的临床特征，遗传病因和病理生理学。我们还将利用最近的技术进步，作为开发这些综合症新型诊断测试的平台。鉴定导致骨髓衰竭的分子途径应提供对调节造血的全球分子途径的见解，并告知我们对普通人群中获得的骨髓衰竭和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允许开发新的诊断测试和合理设计的医疗疗法。阐明遗传骨髓衰竭的分子机制将提供对普通人群中骨髓衰竭的见解。

项目成果

FAM111B Mutation Is Associated With Inherited Exocrine Pancreatic Dysfunction.

• DOI: 10.1097/mpa.0000000000000529
• 发表时间: 2016-07
• 期刊: Pancreas
• 影响因子: 2.9
• 作者: Seo A;Walsh T;Lee MK;Ho PA;Hsu EK;Sidbury R;King MC;Shimamura A
• 通讯作者: Shimamura A