Genetic Analysis of Congenital Diaphragmatic Disorders

The purpose of this study is to understand the genetic causes of congenital diaphragmatic disorders (CDD), namely congenital diaphragmatic hernia (CDH), eventration and hiatal hernia.

Specifically, the investigators plan to:

1. Ascertain informative families and sporadic cases with congenital diaphragmatic disorders and obtain appropriate phenotypic data and genetic material (peripheral blood and/or diaphragm tissue sample).
2. Localize the gene(s) for CDD to specific chromosomal segments using linkage analysis, and determine the role of somatic mutations in CDD.
3. Isolate and characterize genes involved in the pathogenesis of CDD.
4. Develop molecular markers that will facilitate accurate diagnosis (including prenatal diagnosis) and permit correlation of phenotypic variation with specific mutations.
5. Compare RNA-sequencing from tissue samples of children without CDH to those children with CDH.

Study Overview

• Status: Completed
• Conditions: Congenital Diaphragmatic Hernia; Congenital Diaphragmatic Eventration; Congenital Hiatal Hernia; Congenital Diaphragmatic Disorders

• Study Type: Observational
• Enrollment (Actual): 305

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Primary Children's Medical Center
    • Salt Lake City, Utah, United States, 84132
      • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Newborns, children and adults affected by congenital disorders of the diaphragm, such as congenital diaphragmatic hernia, eventration and hiatal hernia.

Description

Inclusion Criteria:

• Diagnosed with a congenital diaphragmatic disorder

Exclusion Criteria:

• none

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genes implicated in CDD can be identified by linkage analysis	Using the Utah Population Database, genes implicated in CDD can be identified by linkage analysis	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Develop molecular markers that will facilitate accurate diagnosis of CDD and CDH.	Develop molecular markers that will facilitate accurate diagnosis (including prenatal diagnosis) and permit correlation of phenotypic variation with specific mutations by localizing the gene(s) for CDH to specific chromosomal segments using linkage analysis in familial cases. In sporadic cases, characterize the role of somatic mutations in CDDs by using a candidate gene approach, and comparative genomic hybridization (CGH) arrays.	5 years

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: Luca Brunelli, MD, University of Utah

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): February 28, 2018
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: November 16, 2010
• First Submitted That Met QC Criteria: November 17, 2010
• First Posted (Estimate): November 18, 2010

Study Record Updates

• Last Update Posted (Actual): April 3, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Congenital Abnormalities; Pathological Conditions, Anatomical; Internal Hernia; Digestive System Abnormalities; Hernia; Hernia, Hiatal; Hernias, Diaphragmatic, Congenital; Hernia, Diaphragmatic; Diaphragmatic Eventration
• Other Study ID Numbers: 35848