title: Evaluation of CAND2 and WNT7a as candidate genes for congenital idiopathic clubfoot.
abstract: Congenital idiopathic clubfoot is a common pediatric musculoskeletal deformity with no known etiology. The deformity reportedly follows a Mendelian pattern of inheritance. Recent work has demonstrated linkage in chromosome 3 and 13 in a large, multigeneration, highly penetrant family with idiopathic clubfoot. From the linkage region on chromosome 3, we selected the candidate genes CAND2 and WNT7a, which are involved in lower extremity development, and hypothesized mutations in these genes would be associated with the phenotype of congenital idiopathic clubfoot. The CAND2 gene was sequenced in 256 clubfoot patients, and 75 control patients, while WNT7a was screened using 56 clubfoot patients and 50 control patients. We found a polymorphism in each gene, but the single nucleotide change in CAND2 was a silent mutation that did not alter the amino acid product, and the single nucleotide change in WNT7a was in the upstream, non-coding or promoter region before the start codon. Based on these results it is unlikely CAND2 and WNT7a are the major genes that causes clubfoot, however WNT7a might be one of many genes that could increase susceptibility to develop clubfoot but do not directly cause it.
authors.affiliation: Department of Orthopaedic Surgery and Rehabilitation, University of Iowa, 200 Hawkins Drive, 01023 JPP, Iowa City, IA 52242, USA.
authors.forename: William
authors.initials: W
authors.lastname: Shyy
authors.forename: Frederick
authors.initials: F
authors.lastname: Dietz
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Dobbs
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: Jose A
authors.initials: JA
authors.lastname: Morcuende
mesh_terms: D016022:Case-Control Studies; D003025:Clubfoot / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007484:Iowa; D008923:Missouri; D009124:Muscle Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014157:Transcription Factors; D051153:Wnt Proteins / Q000235:genetics*
chemical_list: C485649:CAND2 protein, human; D009124:Muscle Proteins; D014157:Transcription Factors; C092778:WNT7A protein, human; D051153:Wnt Proteins