Prevalence and penetrance of ZFPM2 mutations and deletions causing congenital diaphragmatic hernia.

Document Type

Article

Publication Date

4-2015

JAX Source

Clin Genet 2015 Apr; 87(4):362-7.

Volume

87

Issue

4

First Page

362

Last Page

367

ISSN

1399-0004

PMID

24702427

Abstract

Zinc finger protein, FOG2 family member 2 (ZFPM2) (previously named FOG2) gene defects result in the highly morbid congenital diaphragmatic hernia (CDH) in humans and animal models. In a cohort of 275 CDH patient exomes, we estimated the prevalence of damaging ZFPM2 mutations to be almost 5%. Genetic analysis of a multigenerational family identified a heritable intragenic ZFPM2 deletion with an estimated penetrance of 37.5%, which has important implications for genetic counseling. Similarly, a low penetrance ZFPM2 frameshift mutation was observed in a second multiplex family. Isolated CDH was the predominant phenotype observed in our ZFPM2 mutation patients. Findings from the patients described herein indicate that ZFPM2 point mutations or deletions are a recurring cause of CDH. Clin Genet 2015 Apr; 87(4):362-7.

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