Exome sequencing identifies ZFPM2 as a cause of familial isolated congenital diaphragmatic hernia and possibly cardiovascular malformations

Eur J Med Genet. 2014 May-Jun;57(6):247-52. doi: 10.1016/j.ejmg.2014.04.006. Epub 2014 Apr 24.

Abstract

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.

Keywords: CDH; Congenital diaphragmatic hernia; Diaphragm eventration; Exome sequencing; ZFPM2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Abnormalities / genetics*
  • Codon, Nonsense
  • DNA Mutational Analysis / methods*
  • DNA-Binding Proteins / genetics*
  • Exome / genetics*
  • Family Health
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Haploinsufficiency
  • Hernias, Diaphragmatic, Congenital / genetics*
  • Heterozygote
  • Humans
  • Male
  • Pedigree
  • Penetrance
  • Transcription Factors / genetics*

Substances

  • Codon, Nonsense
  • DNA-Binding Proteins
  • Transcription Factors
  • ZFPM2 protein, human