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 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.
Watts
Giles D J
GD
Division of Genetics and Metabolism, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Fegan 10, Boston, MA, 02115, USA.
Mehta
Sarju G
SG
Zhao
Chengfeng
C
Ramdeen
Sheena
S
Hamilton
Sara Jane
SJ
Novack
Deborah V
DV
Mumm
Steven
S
Whyte
Michael P
MP
Mc Gillivray
Barbara
B
Kimonis
Virginia E
VE
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
D005819:Genetic Markers