CORE A: RECRUITMENT AND PHENOTYPING CORE ABSTRACT: Although congenital diaphragmatic hernia (CDH) is a common birth defect, it is still relatively rare and requires infrastructure for recruiting, clinically characterizing, and obtaining biospecimens on patients, and is the foundation for the success of this Program Project. By merging two well-established CDH research programs (Massachusetts General Hospital/Boston Children?s Hospital and Columbia/DHREAMS) we have established one of the largest and most carefully characterized CDH cohorts in the world. Collectively, these two studies have enrolled 1500 patients with CDH and 2683 unaffected family members, and ongoing recruitment is expected to enroll 900 additional patients over the course of this 5 year grant. This Core supports the recruitment and consent of participants, collection of extensive phenotypic data including retrospective medical record review and longitudinal clinical follow-up, collection and processing of biospecimens, and management of data and IRB protocols. The specimens collected will be used extensively for all genomic studies proposed in Project I. Furthermore, the detailed phenotyping of human subjects will be instrumental in the interpretation of data derived from mouse models in Projects II and III, and patient-specific cell lines will be used for functional assays in Project III.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD068250-07
Application #
9551658
Study Section
Special Emphasis Panel (ZHD1)
Project Start
Project End
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
7
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
Longoni, Mauro; High, Frances A; Qi, Hongjian et al. (2017) Genome-wide enrichment of damaging de novo variants in patients with isolated and complex congenital diaphragmatic hernia. Hum Genet 136:679-691
High, Frances A; Bhayani, Pooja; Wilson, Jay M et al. (2016) De novo frameshift mutation in COUP-TFII (NR2F2) in human congenital diaphragmatic hernia. Am J Med Genet A 170:2457-61
Loscertales, Maria; Nicolaou, Fotini; Jeanne, Marion et al. (2016) Type IV collagen drives alveolar epithelial-endothelial association and the morphogenetic movements of septation. BMC Biol 14:59
Donahoe, Patricia K; Longoni, Mauro; High, Frances A (2016) Polygenic Causes of Congenital Diaphragmatic Hernia Produce Common Lung Pathologies. Am J Pathol 186:2532-43
Sanford, Ethan L; Choy, Kwong W; Donahoe, Patricia K et al. (2016) MiR-449a Affects Epithelial Proliferation during the Pseudoglandular and Canalicular Phases of Avian and Mammal Lung Development. PLoS One 11:e0149425
Longoni, M; Russell, M K; High, F A et al. (2015) Prevalence and penetrance of ZFPM2 mutations and deletions causing congenital diaphragmatic hernia. Clin Genet 87:362-7
Lundby, Alicia; Rossin, Elizabeth J; Steffensen, Annette B et al. (2014) Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics. Nat Methods 11:868-74
Longoni, Mauro; High, Frances A; Russell, Meaghan K et al. (2014) Molecular pathogenesis of congenital diaphragmatic hernia revealed by exome sequencing, developmental data, and bioinformatics. Proc Natl Acad Sci U S A 111:12450-5
Lage, Kasper (2014) Protein-protein interactions and genetic diseases: The interactome. Biochim Biophys Acta 1842:1971-1980
Russell, Meaghan K; Longoni, Mauro; Wells, Julie et al. (2012) Congenital diaphragmatic hernia candidate genes derived from embryonic transcriptomes. Proc Natl Acad Sci U S A 109:2978-83

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