Discovery: Novel Gene for Musculoskeletal Deformities
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.”
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.