A new form of congenital muscular dystrophy with joint hyperlaxity maps to 3p23-21

• Published in: Brain (London, England : 1878) Vol. 129; no. 8; pp. 2077 - 2084
• Main Authors: Tétreault, M., Duquette, A., Thiffault, I., Bherer, C., Jarry, J., Loisel, L., Banwell, B., D'Anjou, G., Mathieu, J., Robitaille, Y., Vanasse, M., Brais, B.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-08-2006; Oxford Publishing Limited (England)
• Subjects: Adolescent; Adult; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Child; Chromosome Mapping - methods; Chromosomes, Human, Pair 3 - genetics; Collagen Type VI - deficiency; Collagen Type VI - genetics; congenital muscular dystrophy; Diseases of striated muscles. Neuromuscular diseases; family study; Female; Genetic Linkage; Haplotypes; Humans; hyperlaxity; Joint Instability - complications; Joint Instability - genetics; linkage; Male; Medical sciences; Muscle Fibers, Skeletal - pathology; Muscular Dystrophies - complications; Muscular Dystrophies - congenital; Muscular Dystrophies - genetics; Muscular Dystrophies - pathology; Mutation; Neurology; Pedigree; Pharmacology. Drug treatments; Phenotype; Cartography; Neuromuscular diseases; Nervous system diseases; Congenital; Family study; linkage; Joint; Muscular dystrophy; Genetic disease; Osteoarticular system; hyperlaxity; congenital muscular dystrophy; Genetic linkage
• DOI: 10.1093/brain/awl146
• EISSN: 1460-2156
• ISSN: 0006-8950

Congenital muscular dystrophies (CMDS) are a heterogeneous group of disorders. A growing number of CMDS have been found to be associated with joint hyperlaxity. We recruited 14 French–Canadian cases belonging to 11 families affected by a novel autosomal recessive congenital muscular dystrophy with hyperlaxity (CMDH). All cases come from the southwestern part of Quebec, suggesting a new French–Canadian founder effect. All patients present muscle weakness, proximal contractures coexisting with distal joint hyperlaxity. Pathological and genetic studies have excluded that mutations in the three genes coding for collagen VI subunits are responsible for this disease. A genome-wide scan established linkage of two CMDH families to a region on chromosome 3p23-21. Further linkage analysis confirmed that all families are linked to the same region (log of the odds score of 5.3). Haplotype analysis defines a 1.6-cM candidate interval and suggests that two common mutations may account for 78% of carrier chromosomes. This study describes and maps a new form of recessive CMD with joint hyperlaxity distinct from Ullrich and Bethlem myopathies with a founder effect in the French–Canadian population.