Disease relevance of Distal Myopathies

• Limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM), a distal muscular dystrophy, are both caused by mutations in the recently cloned gene dysferlin, gene symbol DYSF [1].
• Mutations in the human caveolin-3 gene (cav-3) on chromosome 3p25 have been described in limb girdle muscular dystrophy, rippling muscle disease, hyperCKemia, and distal myopathy [2].
• The authors describe a patient with sporadic distal myopathy associated with reduced caveolin-3 in muscle fibers in which the muscle atrophy was restricted to the small muscles of the hands and feet [3].
• Filamentous inclusions were seen in 2.7 per 1000 non-IBM biopsies, including familial oculopharyngeal muscular dystrophy with distal myopathy (OPMD-DM), rigid spine syndrome, acid maltase deficiency and amyloid neuropathy [4].
• However, disease-causing defects were not known until recently, when this central sarcomeric protein was associated with human skeletal tibial muscular dystrophy (TMD/LGMD2J), dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) [5].

High impact information on Distal Myopathies

• Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1) [6].
• Recombinations with D14S72 and D14S49 indicate that this distal myopathy locus, MPD1, should lie between these markers [7].
• We have studied a family segregating a form of autosomal dominant distal myopathy (MIM 160500) and containing nine living affected individuals [7].
• Here, we report on a novel heterozygous single adenine insertion mutation (c.5141_5143insA) in a 40-year-old patient with a distal myopathy [8].
• A missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy, and exerts a dominant negative effect on filament formation [9].

Chemical compound and disease context of Distal Myopathies

• Reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase activity and sialylation in distal myopathy with rimmed vacuoles [10].
• BACKGROUND: UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene mutations have been found in patients with distal myopathy with rimmed vacuoles (DMRV) [11].
• High serum levels of creatine kinase: asymptomatic prelude to distal myopathy [12].

Biological context of Distal Myopathies

• This probable localization of a gene for distal myopathy, MPD1, on chromosome 14 should allow other investigators studying distal myopathy families to test this region for linkage in other types of the disease, to confirm linkage or to demonstrate the likely genetic heterogeneity [7].
• Four different phenotypes have been associated with CAV3 mutations: limb girdle muscular dystrophy-1C (LGMD-1C), rippling muscle disease (RMD), and distal myopathy (DM), as well as idiopathic and familial hyperCKemia (HCK) [13].

Anatomical context of Distal Myopathies

• Myotilin is not the causative gene for vocal cord and pharyngeal weakness with distal myopathy (VCPDM) [14].
• Recently, mutations of the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene were reported to cause hereditary inclusion body myopathy and one type of distal myopathy in a world-wide distribution [15].

Gene context of Distal Myopathies

• As such, our current results may be important in understanding the pathogenesis of Cav-3-related muscle diseases, such as limb-girdle muscular dystrophy-1C, distal myopathy, and rippling muscle disease, that are caused by mutations within the human Cav-3 gene [16].
• Mutations in the gene encoding caveolin-3 (CAV3) underlie four distinct disorders of skeletal muscle: the autosomal dominant form of limb-girdle muscular dystrophy type 1C (LGMD-1C), rippling muscle disease (RMD), sporadic and familial forms of hyperCKemia, and distal myopathy [17].
• Laing early onset distal myopathy: slow myosin defect with variable abnormalities on muscle biopsy [18].
• The desmuslin protein interacts with and is closely related to desmin, a protein encoded by a locus mutated in some forms of hereditary distal myopathy [19].
• We examined 19 muscle biopsies from 14 patients with autosomal recessive distal muscular dystrophy (DisMD) histochemically and immunohistochemically to characterize the histologic features of this disease and to determine whether dystrophin and dystrophin-associated proteins (DAPs) are normally present in the muscles of patients with this disorder [20].

References