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© 1994 American Academy of Neurology A rippling muscle disease gene is localized to 1q41Evidence for multiple genesDepartments of Molecular Genetics and Biochemistry, Human Genetics, and Pediatrics (D.A. Stephan and A.B. Chittenden, and Drs. Zhou and Hoffman), University of Pittsburgh School of Medicine, Pittsburgh, PA; the Department of Pediatrics (Dr. Buist), School of Medicine, Oregon Health Sciences University, Portland, OR; and the Department of Neurology (Dr. Ricker), University of Würzburg, Germany.
Rippling muscle disease (RMD) is an inherited disorder of skeletal muscle in which mechanical stimuli provoke electrically silent contractions. Patient symptoms are muscle cramps, pain, and stiffness, particularly during or following exercise. Clinical signs are balling of muscle following percussion and a characteristic lateral rolling movement of muscle occurring after contraction followed by stretching. We report a new 44-member pedigree segregating RMD as an autosomal dominant trait. A genetic linkage study in this family, using a novel approach of testing closely spaced highly polymorphic markers in affected individuals, localized the responsible gene to the distal end of the long arm of chromosome 1 with a maximum multipoint lod score of 3.56 ( Address correspondence and reprint requests to Dr. Eric P. Hoffman, Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Biomedical Science Tower W1211, Pittsburgh, PA 15261. Supported by NIH grant NS28403. Received February 25, 1994. Accepted in final form April 11, 1994.
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= 0). In this family, RMD is localized to a 12-cM region near D1S235. We studied two previously reported German families for linkage to the same locus, and this same area did not cosegregate with the disease, a finding that shows that different genetic defects can cause a similar clinical phenotype (genetic heterogeneity). An understanding of the defect in contraction control within the muscle fibers in this disease may lead to a better understanding of muscle force transduction, intracellular calcium homeostasis, or both. 
