Clinical trial NCT01098929: Gene Mutations and Rescue in Human Congenital Diaphragmatic Hernia
Official title: Gene Mutations and Rescue in Human Congenital Diaphragmatic Hernia
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Congenital Diaphragmatic Hernia
Keywords: genes
genetic
chromosome
chromosome microarray
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Boston Children's Hospital
First posted: 2010-04-05
Enrollment: 1000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children/infants with a congenital diaphragmatic hernia

Women who are currently pregnant with a fetus diagnosed with congenital diaphragmatic hernia

Individuals with a family history of congenital diaphragmatic hernia

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: identify genes associated with CDH
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Patricia Donahoe, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: Jay Wilson, MD
role: PRINCIPAL_INVESTIGATOR
References: