Discovery: Novel Gene for Musculoskeletal Deformities
03/10/2010

St. Louis, MO—Researchers funded by the Children’s Discovery Institute have just published results linking the mutation of a gene to distal arthrogryposis type I, a congenital disorder that causes clubfoot and other deformities of children’s joints.  The gene, MYBPC1, which codes for a protein essential to human muscle, is analyzed in an article in the peer-reviewed journal, Human Molecular Genetics.

“By understanding the genetics of these types of deformities, we can help families understand what is happening to their children,” notes Christina Gurnett, MD, PhD, Assistant Professor of Neurology, Pediatrics, and Orthopedic Surgery at Washington University School of Medicine (WUSM) and a Faculty Scholar in the Children’s Discovery Institute’s Center for Musculoskeletal and Metabolic Diseases. “We also provide avenues for the study of new, genetically targeted therapies.”

Dr. Gurnett is the first author on the new publication. Coauthors are two other Institute investigators—Matthew Dobbs, MD, Associate Professor of Orthopedic Surgery at WUSM and Todd Druley, MD, PhD, of the university’s Department of Pediatrics—along with several other WUSM scientists. Support from the Children’s Discovery Institute encourages this kind of collaborative, interdisciplinary research, which fosters innovation in pediatric health science.

A family disease

In the published study, Dr. Gurnett and her team describe five generations of a family with hereditary distal arthrogryposis type I. Genetic information on the family resides in a DNA data bank of musculoskeletal disorders that Dr. Gurnett has developed through funding from the Children’s Discovery Institute.

Gene mapping of 12 members of this family revealed mutations of the MYBPC1gene. In another family, a different mutation to the MYBPC1 gene was identified. All the mutations were associated with poor development of a type of muscle fiber, which helps to explain the joint contraction and stiffness that occurs in the hands and feet of patients born with distal arthrogryposis.

This study may pave the way for future forms of treatment or prevention for distal arthrogryposis, which modify MYBPC1 pathways. In the meantime, says Dr. Gurnett, “ it is great to be able to give families a genetic diagnosis.  It gives them a sense of closure, explains why the deformity occurs, and helps them come to terms with risks to future generations.”
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Christina A. Gurnett, David M. Desruisseau, Kevin McCall, Ryan Choi, Zachary I. Meyer,  Michael Talerico, Sara E. Miller, Jeong-Sun Ju,  Alan Pestronk, Anne M. Connolly, Todd E. Druley, Conrad C. Weihl, and Mathew B. Dobbs. Myosin binding protein C1: a novel gene for autosomal dominant distal arthrogryposis type 1. Hum Molec Genet. 2010. To read an abstract of this article on distal arthrogryposis and MYBPC1 mutations, click here.