Clinical & Molecular Characterization of Collagen VI Myopathies
Congenital muscular dystrophies are a genetically diverse group of disorders resulting in muscle weakness with or without joint contractures. Collagen VI myopathies include two disorders, Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM). These disorders had initially been considered distinct, but have since been connected to the three genes that encode collagen VI (review at genetests.org). Both disorders share an unusual combination of laxity in some joints with contractures in others.
UCMD is a relatively severe disorder with onset in young infants and children. Symptoms include neonatal hypotonia, progressive weakness, proximal joint contractures and laxity of distal joints. BM is a milder syndrome characterized by slowly progressive proximal weakness and contractures in distal joints with onset in the first or second decade. Once thought to be quite rare, it has become increasingly clear that congenital myopathy and muscular dystrophy phenotypes due to mutations in collagen VI are among the more common causes of inherited muscle weakness. Collagen VI is made from three separate genes, COL6A1 and COL6A2 on chromosome 21 and COL6A3 on chromosome 2. These genes encode the three peptide chains which form collagen VI. These three peptide chains undergo a complex assembly process before being excreted from the cell and forming a complex network of microfibrils. It is thought that collagen VI plays an important role in linking the internal structure of the cell to the extracellular matrix.
Related articles about Collagen VI Mypoathies from the Catalog of Human Genes and Genetic Diosrders:
Genetic testing for BM and UCMD has been available at the Utah Genome Center. While the number of identified mutations in the COL6A genes is accumulating, it is difficult to predict the outcome of any specific mutation. Substantial variation exists between patients with collagen VI myopathies, even in patients with similar mutations. In order to clarify the relationship between a particular mutation and its manifestations in disease, we have recently started enrolling patients in a database to catalog detailed genetic and clinical information from patients with collagen VI myopathies, including Bethlem Myopathy and Ullrich congenital muscular dystrophy.The goals of this project are the following:
- Establishment of a database containing detailed genotype and phenotype from collagen VI myopathy patients
- Develop testable hypotheses as to the molecular pathogenesis of these disorders based on the available genotype and phenotype data
- Assist in the identification of well characterized cohorts of patients who will be candidates for clinical trials in the future
- Facilitate interactions between patients, families and researchers in the field
For more information contact the following:
Russell Butterfield, MD, PhD
Pediatric Motor Disorders Research Program
University of Utah, School of Medicine
Departments of Neurology and Pediatrics