Analysis of FOXF1 and the FOX gene cluster in patients with VACTERL association

Eur J Med Genet. 2011 May-Jun;54(3):323-8. doi: 10.1016/j.ejmg.2011.01.007. Epub 2011 Feb 26.


VACTERL association, a relatively common condition with an incidence of approximately 1 in 20,000 -35,000 births, is a non-random association of birth defects that includes vertebral defects (V), anal atresia (A), cardiac defects (C), tracheo-esophageal fistula (TE), renal anomalies (R) and limb malformations (L). Although the etiology is unknown in the majority of patients, there is evidence that it is causally heterogeneous. Several studies have shown evidence for inheritance in VACTERL, implying a role for genetic loci. Recently, patients with component features of VACTERL and a lethal developmental pulmonary disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), were found to harbor deletions or mutations affecting FOXF1 and the FOX gene cluster on chromosome 16q24. We investigated this gene through direct sequencing and high-density SNP microarray in 12 patients with VACTERL association but without ACD/MPV. Our mutational analysis of FOXF1 showed normal sequences and no genomic imbalances affecting the FOX gene cluster on chromosome 16q24 in the studied patients. Possible explanations for these results include the etiologic and clinical heterogeneity of VACTERL association, the possibility that mutations affecting this gene may occur only in more severely affected individuals, and insufficient study sample size.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Adolescent
  • Adult
  • Anal Canal / abnormalities
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 16 / genetics*
  • DNA Mutational Analysis
  • Esophagus / abnormalities
  • Female
  • Forkhead Transcription Factors / genetics*
  • Heart Defects, Congenital
  • Humans
  • Infant
  • Kidney / abnormalities
  • Limb Deformities, Congenital
  • Male
  • Microarray Analysis / methods
  • Multigene Family*
  • Polymorphism, Single Nucleotide
  • Spine / abnormalities
  • Trachea / abnormalities


  • FOXF1 protein, human
  • Forkhead Transcription Factors

Supplementary concepts

  • VACTERL association