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

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.

SUBMITTER: Longoni M

PROVIDER: S-EPMC4410767 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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

Longoni M M Russell M K MK High F A FA Darvishi K K Maalouf F I FI Kashani A A Tracy A A AA Coletti C M CM Loscertales M M Lage K K Ackerman K G KG Woods S A SA Ward-Melver C C Andrews D D Lee C C Pober B R BR Donahoe P K PK

Clinical genetics 20140426 4

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 l ...[more]

PMID: 24702427

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