Prevalence and penetrance of ZFPM2 mutations and deletions causing congenital diaphragmatic hernia.
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.
The Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA, USA; Department of Surgery.
M
M
Longoni
M K
MK
Russell
F A
FA
High
K
K
Darvishi
F I
FI
Maalouf
A
A
Kashani
A A
AA
Tracy
C M
CM
Coletti
M
M
Loscertales
K
K
Lage
K G
KG
Ackerman
S A
SA
Woods
C
C
Ward-Melver
D
D
Andrews
C
C
Lee
B R
BR
Pober
P K
PK
Donahoe
D001483:Base Sequence; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D004268:DNA-Binding Proteins / Q000235:genetics*; D059472:Exome / Q000235:genetics; D065630:Hernias, Diaphragmatic, Congenital / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D019683:Penetrance; D010641:Phenotype; D015995:Prevalence; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C117427:ZFPM2 protein, human
DNA copy number variation; FOG2; ZFPM2; congenital diaphragmatic hernia; exome; penetrance