title: Mapping autosomal dominant progressive limb-girdle myopathy with bone fragility to chromosome 9p21-p22: a novel locus for a musculoskeletal syndrome.
abstract: 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.
authors.affiliation: Division of Genetics and Metabolism, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Fegan 10, Boston, MA, 02115, USA.
authors.forename: Giles D J
authors.initials: GD
authors.lastname: Watts
authors.forename: Sarju G
authors.initials: SG
authors.lastname: Mehta
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Zhao
authors.forename: Sheena
authors.initials: S
authors.lastname: Ramdeen
authors.forename: Sara Jane
authors.initials: SJ
authors.lastname: Hamilton
authors.forename: Deborah V
authors.initials: DV
authors.lastname: Novack
authors.forename: Steven
authors.initials: S
authors.lastname: Mumm
authors.forename: Michael P
authors.initials: MP
authors.lastname: Whyte
authors.forename: Barbara
authors.initials: B
authors.lastname: Mc Gillivray
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Kimonis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D005260:Female; D050723:Fractures, Bone / Q000209:etiology / Q000235:genetics*; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D010375:Pedigree
chemical_list: D005819:Genetic Markers