title: Analysis of FOXF1 and the FOX gene cluster in patients with VACTERL association.
abstract: 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.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Building 35, Room 1B207, 35 Convent Drive MSC 3717, Bethesda, MD 20892-3717, United States. nneamaka.agochukwu@nih.gov
authors.forename: Nneamaka B
authors.initials: NB
authors.lastname: Agochukwu
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Pineda-Alvarez
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Keaton
authors.forename: Nicole
authors.initials: N
authors.lastname: Warren-Mora
authors.forename: Manu S
authors.initials: MS
authors.lastname: Raam
authors.forename: Aparna
authors.initials: A
authors.lastname: Kamat
authors.forename: Settara C
authors.initials: SC
authors.lastname: Chandrasekharappa
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Solomon
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D001003:Anal Canal / Q000002:abnormalities; D002648:Child; D002675:Child, Preschool; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004947:Esophagus / Q000002:abnormalities; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006330:Heart Defects, Congenital; D006801:Humans; D007223:Infant; D007668:Kidney / Q000002:abnormalities; D017880:Limb Deformities, Congenital; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D013131:Spine / Q000002:abnormalities; D014132:Trachea / Q000002:abnormalities
chemical_list: C098521:FOXF1 protein, human; D051858:Forkhead Transcription Factors