Exome sequencing identifies ZFPM2 as a cause of familial isolated congenital diaphragmatic hernia and possibly cardiovascular malformations.
Using exome sequencing we identify a heterozygous nonsense mutation in ZFPM2 as a cause of familial isolated congenital diaphragmatic hernia in 2 affected siblings. This mutation displays variable phenotypic expression being present in a third sibling with a mild diaphragmatic eventration and a cardiovascular malformation. The same variant is seen in 2 additional family members, both of whom are asymptomatic, thus highlighting that ZFPM2 haploinsufficiency is associated with reduced penetrance. Our finding adds further evidence for ZFPM2 having a role in diaphragm and cardiovascular development.
Centre for Human Genetics, KU Leuven, University Hospital Leuven, Belgium.
Paul D
PD
Brady
Centre for Human Genetics, KU Leuven, University Hospital Leuven, Belgium.
Jeroen
J
Van Houdt
Department of Pediatrics and Medical Genetics, Universiteit Gent, Gent, Belgium.
Bert
B
Callewaert
Department of Development and Regeneration, Unit Pregnancy, Foetus and Newborn, KU Leuven, Belgium; Department Obstetrics and Gynaecology, University Hospital Leuven, Belgium.
Jan
J
Deprest
Centre for Human Genetics, KU Leuven, University Hospital Leuven, Belgium.
Koenraad
K
Devriendt
Centre for Human Genetics, KU Leuven, University Hospital Leuven, Belgium.
Joris R
JR
Vermeesch
D018376:Cardiovascular Abnormalities / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis / Q000379:methods*; D004268:DNA-Binding Proteins / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D057895:Haploinsufficiency; D065630:Hernias, Diaphragmatic, Congenital / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D019683:Penetrance; D014157:Transcription Factors / Q000235:genetics*
D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C117427:ZFPM2 protein, human
CDH; Congenital diaphragmatic hernia; Diaphragm eventration; Exome sequencing; ZFPM2