TY - JOUR
T1 - Mapping of autosomal dominant progressive myopathy of a limb-girdle distribution and bone fragility to chromosome 9p21-22: Identification of a novel locus for a musculoskeletal syndrome
AU - Watts, Giles D.
AU - Mehta, Sarju G.
AU - Zhao, Chengfeng
AU - Ramdeen, Sheena
AU - Hamilton, Sara Jane
AU - Novack, Deborah V.
AU - Mumm, Steven
AU - Whyte, Michael P.
AU - McGillivray, Barbara
AU - Kimonis, Virginia E.
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
U2 - 10.1007/s00439-005-0075-z
DO - 10.1007/s00439-005-0075-z
M3 - Article
VL - 118
SP - 508
EP - 514
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 3-4
ER -