Gene Mutations and Rescue in Human Congenital Diaphragmatic Hernia

Study Overview
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Brief Summary
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Congenital diaphragmatic hernia (CDH) occurs when the diaphragm, the muscle that separates the chest cavity from the abdominal cavity, does not form properly. When an opening is present in the diaphragm, organs that are normally found in the abdomen can move up into the chest cavity. The primary objective of this study is to generate information about the hereditary basis of congenital diaphragmatic hernia and abnormal lung development. Our long-term goal is to identify ways to treat babies in utero with effective but safe drugs to speed up lung development before birth.

Detailed Description
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This study uses a combination of clinical, molecular biological, and developmental strategies to better understand the genetic basis of congenital diaphragmatic hernia. Ongoing projects at Massachusetts General Hospital include identification of novel genes affecting diaphragm and lung development in a) mouse models using laser capture, microdissection, expression arrays, and statistical and bioinformatics analysis and b) human kindreds with multiple affected family members using linkage analysis and exome sequencing. Research projects based at Children's Hospital Boston include a) continued recruitment of a population of patients with congenital diaphragmatic hernia who are carefully phenotyped for entry into an extensive database, b) collection of biological samples belonging to the phenotyped cohort of patients, c) next-generation sequencing on candidate genes and d) molecular cytogenetic studies such as comparative genomic hybridization and subtelomeric fluorescence in situ hybridization. Over 500 patients with congenital diaphragmatic hernia and their families have been recruited to date and efforts are ongoing to double this number. The investigators hope that the information gained through identifying the genes that contribute to congenital diaphragmatic hernia will provide the foundation for future efforts to develop effective interventions for the treatment of this disease.

Official Title
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Gene Mutations and Rescue in Human Congenital Diaphragmatic Hernia

Conditions
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Congenital Diaphragmatic Hernia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All individuals affected with a congenital diaphragmatic hernia (CDH), or with a family history of CDH Exclusion Criteria: Individuals with no personal or family history of a CDH
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Congenital Diaphragmatic Hernia (CDH)<br>Individuals affected with congenital diaphragmatic hernia (CDH) | |
| Unaffected<br>Healthy family members of individuals affected with congenital diaphragmatic hernia (CDH) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| identify genes associated with CDH |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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genes, genetic, chromosome, chromosome microarray