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Updated: Sep 3, 2025
Transuterine Fetal Tracheal Occlusion Model in Mice
Published on: February 5, 2021
Identifying phenotypic expansions for congenital diaphragmatic hernia plus (CDH+) using DECIPHER data
Amy Hardcastle1, Aliska M Berry2, Ian M Campbell3
1Department of Microbiology and Molecular Biology, College of Life Sciences, Brigham Young University, Provo, Utah, USA.
Insights
Identifying genes involved in congenital diaphragmatic hernia (CDH) is crucial. This study highlights CREBBP, SMARCA4, UBA2, and USP9X as potential contributors to CDH development.
Area of Science:
- Genetics
- Developmental Biology
- Medical Research
Background:
- Congenital diaphragmatic hernia (CDH) is a birth defect with an often unknown molecular cause.
- Understanding genes involved in diaphragm development is key to identifying CDH etiologies.
- CDH can occur alone or with other birth defects (CDH+).
Purpose of the Study:
- To identify genes potentially involved in diaphragm development using data from individuals with CDH+.
- To discover new phenotypic expansions associated with CDH.
- To leverage public databases for genetic research in rare diseases.
Main Methods:
- Analysis of clinical and molecular data from 36 individuals with CDH+ in the DECIPHER database.
- Identification of deleterious sequence or copy number variants in candidate genes.
- Validation of gene function through expression data in developing mouse diaphragms and machine learning algorithms.
Main Results:
- Deleterious variants in CREBBP, SMARCA4, UBA2, and USP9X were identified in individuals with CDH+.
- These genes are expressed in the developing mouse diaphragm.
- The identified genes show similarity to known CDH-associated genes.
Conclusions:
- CREBBP, SMARCA4, UBA2, and USP9X are suggested to play a role in diaphragm development.
- Public databases like DECIPHER are valuable for identifying new CDH-related genes and phenotypes.
- Further research into these genes may improve understanding and diagnosis of CDH.
Abstract:
Congenital diaphragmatic hernia (CDH) can occur in isolation or in conjunction with other birth defects (CDH+). A molecular etiology can only be identified in a subset of CDH cases. This is due, in part, to an incomplete understanding of the genes that contribute to diaphragm development. Here, we used clinical and molecular data from 36 individuals with CDH+ who are cataloged in the DECIPHER database to identify genes that may play a role in diaphragm development and to discover new phenotypic expansions. Among this group, we identified individuals who carried putatively deleterious sequence or copy number variants affecting CREBBP, SMARCA4, UBA2, and USP9X. The role of these genes in diaphragm development was supported by their expression in the developing mouse diaphragm, their similarity to known CDH genes using data from a previously published and validated machine learning algorithm, and/or the presence of CDH in other individuals with their associated genetic disorders. Our results demonstrate how data from DECIPHER, and other public databases, can be used to identify new phenotypic expansions and suggest that CREBBP, SMARCA4, UBA2, and USP9X play a role in diaphragm development.
