Gene Mutation and Rescue in Human Diaphragmatic Hernia

2p01-hd068250的行政补充

ADMINISTRATIVE SUPPLEMENT TO 2P01-HD068250 ABSTRACT: Congenital diaphragmatic hernia (CDH) is a common birth defect, which requires considerable infrastructure for creating and maintaining multi-institutional single IRBs, recruiting, clinically characterizing, obtaining, processing, and maintaining biospecimens on patients, with research centered at the Massachusetts General Hospital, Boston Children’s, and Columbia University, New York from 16 different clinical centers. The carefully honed infrastructure for patients, specimens, and data is the foundation for the success of this Program Project, “Gene Mutation and Rescue in Human Diaphragmatic Hernia”, to study genetic contributions to the structural birth defect, CDH. We have established one of the largest and most carefully characterized CDH cohorts in the world, which this Administrative Supplement aims to preserve. Collectively, we have already enrolled 2045 patients with CDH and 3662 unaffected family members, and ongoing recruitment has been expected to enroll 100 – 150 patients and families per year over the course of the Administrative Supplement, which will support the follow on recruitment and consent of participants, the continued collection and organization of extensive phenotypic data including retrospective medical record review and longitudinal clinical followup, follow on collection and processing of specimens with preservation of existing biospecimens, and data management by high quality bioinformatic analyses and annotation of genomic and phenotyping data. The data has been sequenced by the Broad Institute of Harvard and MIT but not yet released by the Data Release Resource at the University of Pennsylvania. This data must then be analyzed, then shared with dbGAP and Gabriella Miller Kid’s First Program portals to preserve data and specimens for this precious resource. The detailed phenotyping of human subjects will be instrumental in the interpretation of data derived by us and other investigators of the broad research community. Protecting the resource for posterity is uppermost in our Aims since we have invested considerable expertise and NICHD has invested millions of dollars into this Project under the auspices of the Structural Birth Defects Program of the NICHD.