Genetic abnormalities in FOXP1 are associated with congenital heart defects

Sheng Wei Chang, Mona Mislankar, Chaitali Misra, Nianyuan Huang, Daniel G. Dajusta, Steven M. Harrison, Kim L. Mcbride, Linda A. Baker, Vidu Garg

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


The etiology for the majority of congenital heart defects (CHD) is unknown. We identified a patient with unbalanced atrioventricular septal defect (AVSD) and hypoplastic left ventricle who harbored an ∼0.3 Mb monoallelic deletion on chromosome 3p14.1. The deletion encompassed the first four exons of FOXP1, a gene critical for normal heart development that represses cardiomyocyte proliferation and expression of Nkx2.5. To determine whether FOXP1 mutations are found in patients with CHD, we sequenced FOXP1 in 82 patients with AVSD or hypoplastic left heart syndrome. We discovered two patients who harbored a heterozygous c.1702C>T variant in FOXP1 that predicted a potentially deleterious substitution of a highly conserved proline (p.Pro568Ser). This variant was not found in 287 controls but is present in dbSNP at a 0.2% frequency. The orthologous murine Foxp1 p.Pro596Ser mutant protein displayed deficits in luciferase reporter assays and resulted in increased proliferation and Nkx2.5 expression in cardiomyoblasts. Our data suggest that haploinsufficiency of FOXP1 is associated with human CHD.

Original languageEnglish (US)
Pages (from-to)1226-1230
Number of pages5
JournalHuman mutation
Issue number9
StatePublished - Sep 2013


  • Atrioventricular septal defect
  • Cardiomyocyte
  • FOXP1
  • Hypoplastic left heart syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Genetic abnormalities in FOXP1 are associated with congenital heart defects'. Together they form a unique fingerprint.

Cite this