Mapping autosomal dominant progressive limb-girdle myopathy with bone fragility to chromosome 9p21-p22 : a novel locus for a musculoskeletal syndrome

Progressive myopathy of a limb-girdle distribution and bone fragility is a rare autosomal dominant disorder of unknown etiology. Affected individuals, within this family, present with various combinations of progressive muscle weakness, easy fracturing, and poor healing of long bones. Additional fea...

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Bibliographic Details
Published in:Human genetics 2005-12, Vol.118 (3-4), p.508-514
Main Authors: WATTS, Giles D. J, MEHTA, Sarju G, CHENGFENG ZHAO, RAMDEEN, Sheena, HAMILTON, Sara Jane, NOVACK, Deborah V, MUMM, Steven, WHYTE, Michael P, MCGILLIVRAY, Barbara, KIMONIS, Virginia E
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Biological and medical sciences
Biopsy
Bone diseases
Chromosome Mapping
Chromosomes
Chromosomes, Human, Pair 9
Classical genetics, quantitative genetics, hybrids
Complex syndromes
Female
Fractures
Fractures, Bone - etiology
Fractures, Bone - genetics
Fundamental and applied biological sciences. Psychology
Genetic Markers
Genetics
Genetics of eukaryotes. Biological and molecular evolution
Genomes
Genomics
Haplotypes
Hernia
Hospitals
Human
Humans
Inheritance Patterns
Kinases
Male
Males
Medical colleges
Medical genetics
Medical sciences
Methods, theories and miscellaneous
Middle Aged
Muscular Dystrophies, Limb-Girdle - genetics
Muscular Dystrophies, Limb-Girdle - pathology
Muscular Dystrophies, Limb-Girdle - physiopathology
Muscular dystrophy
Pedigree
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Summary:Progressive myopathy of a limb-girdle distribution and bone fragility is a rare autosomal dominant disorder of unknown etiology. Affected individuals, within this family, present with various combinations of progressive muscle weakness, easy fracturing, and poor healing of long bones. Additional features include premature graying with thin hair, thin skin, hernias, and clotting disorders. Electromyograms show myopathic changes and biopsies reveal non-specific myopathic changes. Skeletal radiographs demonstrate coarse trabeculation, patchy sclerosis, cortical thickening, and narrowing of medullary cavities. We report genetic mapping of this disorder to chromosome 9p21-p22 in a multigenerational family. A genome-wide scan for the disease locus obtained a maximal LOD score of 3.74 for marker GATA87E02 N (D9S1121). Haplotype analysis localized the disease gene within a 15 Mb interval flanked by markers AGAT142P and GATA5E06P. This region also localizes diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH). Identification of the disease gene will be necessary to understand the pathogenesis of this complex disorder.
ISSN:0340-6717
1432-1203
DOI:10.1007/s00439-005-0075-z