Logo image
Back
Evaluation of embryonic and perinatal myosin gene mutations and the etiology of congenital idiopathic clubfoot
Journal article   Open access   Peer reviewed

Evaluation of embryonic and perinatal myosin gene mutations and the etiology of congenital idiopathic clubfoot

William Shyy, Kai Wang, Val C Sheffield and Jose A Morcuende
Journal of pediatric orthopaedics, Vol.30(3), pp.231-234
04/2010
DOI: 10.1097/BPO.0b013e3181d35e3f
PMCID: PMC2913130
PMID: 20357587
url
http://doi.org/10.1097/BPO.0b013e3181d35e3fView
Open Access

Abstract

Congenital idiopathic clubfoot is the most common musculoskeletal birth defect that develops during the fetal period, but with no known etiology. MYH 2, 3, 7, and 8 are expressed embryonically or perinatally, the period during which congenital idiopathic clubfoot develops; are all components of Type II muscle, which is consistently decreased in clubfoot patients; and are associated with several muscle contracture syndromes that have associated clubfoot deformities. In this study, we hypothesized that a mutation in an embryonic or perinatal myosin gene could be associated with congenital idiopathic clubfoot. We screened the exons, splice sites, and predicted promoters of 24 bilateral congenital idiopathic clubfoot patients and 24 matched controls in MYH 1, 2, 3, and 8 via sequence-based analysis, and screened an additional 76 patients in each discovered SNP. Although many single-nucleotide polymorphisms were found; none proved to be significantly associated with the phenotype of congenital idiopathic clubfoot. Also, no known mutations that cause distal arthrogryposis syndromes were found in the congenital idiopathic clubfoot patients. These findings demonstrate that congenital idiopathic clubfoot has a different pathophysiology than the clubfoot seen in distal arthrogryposis syndromes, and defects in myosin are most likely not directly responsible for the development of congenital clubfoot. Given the complexity of early myogenesis, many regulatory candidate genes remain that could cause defects in the hypaxial musculature that is invariably observed in congenital idiopathic clubfoot. This study further differentiates congenital idiopathic clubfoot as distinct from other complex genetic syndromes that can present with similar deformities, and thus facilitates further research to improve the clinical diagnosis and treatment of congenital idiopathic clubfoot.
 Clubfoot - physiopathology Clubfoot - genetics Genetic Predisposition to Disease Exons Humans Myosin Heavy Chains - genetics Female Male Polymorphism, Single Nucleotide Mutation Sequence Analysis, DNA Case-Control Studies

Details

Metrics

31 Record Views
19 Times Cited - Web of Science
Logo image