ABSTRACT
Emery-Dreifuss muscular dystrophy (EDMD), a rare inherited disease, is characterized clinically by humero-peroneal muscle atrophy and weakness, multijoint contractures, spine rigidity and cardiac insufficiency with conduction defects. There are at least six types of EDMD known so far, of which five have been associated with mutations in genes encoding nuclear proteins. The majority of the EDMD cases described so far are of the emerinopathy (EDMD1) kind, with a recessive X-linked mode of inheritance, or else laminopathy (EDMD2), with an autosomal dominant mode of inheritance. In the work described here, the authors have sought to describe the history by which EDMD came to be distinguished as a separate entity, as well as the clinical and genetic characteristics of the disease, the pathophysiology of lamin-related muscular diseases and, finally, therapeutic issues, prevention and ethical aspects.
Subject(s)
Genetic Predisposition to Disease , Muscular Atrophy/genetics , Muscular Atrophy/pathology , Muscular Dystrophy, Emery-Dreifuss/genetics , Muscular Dystrophy, Emery-Dreifuss/pathology , Mutation/genetics , Animals , Humans , Muscle Cells/pathology , Muscular Atrophy/diagnosis , Muscular Atrophy/physiopathology , Muscular Dystrophy, Emery-Dreifuss/diagnosis , Nuclear Proteins/genetics , Nuclear Proteins/metabolismABSTRACT
The study demonstrates a 12-year-old patient with progressive proximal muscle weakness, joint contractures, rigidity of the neck, and absence of emerin and lamin A in the muscle nuclei, which is caused by intronic mutation IVS3-27del18 (c.266-27del18) in the emerin gene. The most surprising finding was the appearance of IBM-like inclusions in euchromatin, as well as aberrant nuclei. It may be speculated that altered expression of the emerin-lamin complex and modification of the nuclear matrix leads to formation of tubulofilamentous structures in the presented case.
Subject(s)
Inclusion Bodies/ultrastructure , Lamin Type A/deficiency , Muscular Dystrophy, Emery-Dreifuss/genetics , Muscular Dystrophy, Emery-Dreifuss/metabolism , Muscular Dystrophy, Emery-Dreifuss/pathology , Blotting, Western , Child , Child, Preschool , DNA Mutational Analysis , Humans , Male , Membrane Proteins/genetics , Microscopy, Electron, Transmission , Muscle, Skeletal/metabolism , Muscle, Skeletal/ultrastructure , Mutation , Nuclear Proteins/genetics , Polymerase Chain ReactionABSTRACT
This paper is a part of an introduction to authors' study on systemic laminopathies and their role in human aging. Of special interest is progeria--a type of systemic laminopathy associated usually with mutation 1824 C > T and presenting phenotype of preliminary aging. The authors analyse the differences between the progeria and other syndrome of preliminary aging--Werner's syndrome.
