1. Late-onset autosomal dominant limb girdle muscular dystrophy and Paget's disease of bone unlinked to the VCP gene locus
- Author
-
Michael Kottlors, Markus Heitzer, Janbernd Kirschner, Antje Bornemann, Ralf Schwarzwald, Verena Haug, Klaus Mueller, Angela Huebner, Olaf Moske-Eick, Wolfram Kress, and Sabine Krause
- Subjects
Adult ,Male ,medicine.medical_specialty ,Valosin-containing protein ,Cell Cycle Proteins ,Myotonic dystrophy ,Valosin Containing Protein ,Internal medicine ,Germany ,medicine ,Facioscapulohumeral muscular dystrophy ,Humans ,Family ,Muscular dystrophy ,Age of Onset ,Myopathy ,Muscle, Skeletal ,Adenosine Triphosphatases ,Leg ,Muscle biopsy ,biology ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Osteitis Deformans ,Pedigree ,Paget's disease of bone ,Endocrinology ,Phenotype ,Neurology ,Muscular Dystrophies, Limb-Girdle ,Mutation ,biology.protein ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Limb-girdle muscular dystrophy - Abstract
The broadwide spectrum of differential diagnoses of autosomal dominant muscular dystrophies in adults can be specified by additional features. The combination of late-onset muscular dystrophy, rimmed vacuoles and inclusion bodies in the muscle biopsy, and Paget's disease of bone suggests a mutation in the Valosin-containing protein gene (VCP, p97 or CDC48) even without dementia. We report on a German family with late-onset autosomal dominant muscular dystrophy starting in the pelvic girdle about age 40years, a subsequent rapidly-progressing course, high alkaline phosphatase and Paget's disease of bone. Clinical examination revealed no cognitive impairment. Histology showed myopathic changes with rimmed vacuoles and inclusion bodies on muscle biopsy. Mutations in VCP, filamin C, desmin, alphaB-crystallin, ZASP and myosin heavy chains 2 and 7 as well as the genes for facioscapulohumeral muscular dystrophy, Myotonic Dystrophy I and II, and LGMD1A-G were excluded by a combination of linkage analysis and direct sequencing. The family presented here suggests that a yet-unknown genetic defect can give rise to an autosomal dominant myopathy with Paget's disease but without dementia.
- Published
- 2009