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Evaluation of CAND2 and WNT7a as Candidate Genes for Congenital Idiopathic Clubfoot

  • Symposium: Clubfoot: Etiology and Treatment
  • Published:
Clinical Orthopaedics and Related Research

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.

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Acknowledgments

We thank Matthew Sinnwell for technical assistance, the University of Iowa Hospitals and Clinics Departments of Orthopaedics and Pediatrics, and the University of Iowa Carver College of Medicine research program.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery and Rehabilitation, University of Iowa, 200 Hawkins Drive, 01023 JPP, Iowa City, IA, 52242, USA

    William Shyy BA, Frederick Dietz MD & Jose A. Morcuende MD, PhD

  2. Department of Orthopaedic Surgery, Washington University, St. Louis, MO, USA

    Matthew B. Dobbs MD

  3. Department of Pediatrics, University of Iowa, Iowa City, IA, USA

    Val C. Sheffield MD, PhD

Authors
  1. William Shyy BA
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  2. Frederick Dietz MD
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  3. Matthew B. Dobbs MD
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  4. Val C. Sheffield MD, PhD
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  5. Jose A. Morcuende MD, PhD
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Corresponding author

Correspondence to Jose A. Morcuende MD, PhD.

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Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that his or her institution has approved the animal and human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.

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Shyy, W., Dietz, F., Dobbs, M.B. et al. Evaluation of CAND2 and WNT7a as Candidate Genes for Congenital Idiopathic Clubfoot. Clin Orthop Relat Res 467, 1201–1205 (2009). https://doi.org/10.1007/s11999-008-0701-x

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  • DOI: https://doi.org/10.1007/s11999-008-0701-x

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