The Study Of Clinical Features, Pathology, Emerin And The Expression Of STA Gene In Patients With Emery-Dreifuss Muscular Dystrophy

Emery-Dreifuss muscular dystrophy (EDMD) is a special kind of infrequent primary muscular dystrophy and it was identified as an independent hereditary muscular disease in 1996. The STA gene, which was responsible for X-linked EDMD form, was identified in 1994. The LMNA gene responsible for autosomal dominant EDMD form was identified in 1999. Emery-Dreifuss muscular dystrophy is characterized by the triad of (1) early contractures of elbows, Achilles tendons and post-cervical muscles (entire spine); (2) slowly progressive muscle wasting and weakness with a distinctive humero-peroneal distribution; and (3) cardiac conduction defects leading to dilated cardiomyopahty. Thus affected individuals may die suddenly from arrhythmia.Two main modes of inheritance exist: X-linked and autosomal dominant. Rare autosomal recessive inheritance has also been described. Most X-linked EDMD patients become symptomatic in early childhood (<15 years) with mild weakness, followed by contractures. The disease is usually progressing and has a moderately benign course; loss of ambulation is exceptional. The disease course of the AD-EDMD is generally slow, but we can observe milder phenotype characterized by late onset and a mild degree of weakness and contractures or more severe phenotype with early presentation and a rapidly progressive course in few cases. It seems to be somewhat more severe than X-linked EDMD. A marked inter- and intra-familial variability in the clinical expression exists in patients with AD-EDMD. And some patients may have no inherited background at all.The diagnosis of EDMD is based just on clinical observation because there is no characteristic distinction in muscle biopsies. Immunohistochemistry of muscle biopsy tissue, leucocytes, fibroblasts or exfoliative buccal cells for emerin (X-linked EDMD), can confirm the diagnosis.Material and MethodsThe patients were divided into three groups: Experiment EDMD group (Emery-Dreifuss muscular dystrophy patients), control LGMD group (the limb girdle muscular dystrophy patient) and FSHD group (the facioscapulohumeral muscular dystrophy patients). After the EDMD patient died for 10 hours, we observed the tissues from cerebrum, cerebellum, heart, sciatic nerve, biceps brachii muscle, quadriceps femoris, gastrocnemius muscle,and tibialis anterior muscle removed at necropsy by microscopy. At the same time, we observed the ultrastructure of skeletal muscles sarcolemma by electron microscopy. Total DNA was extracted from every patient's venous blood, the products amplified by polymerase chain reaction (PCR) method were purified and then served for sequencing. Monoclonal antibody was used to check for emerin by immunohistochemistry of skeletal muscle samples and non-muscle tissues. ResultsFrozen sections from EDMD patient's skeletal muscles showed increased variability in muscle fiber size and round fiber. Part of muscle fibers was replaced by adipose tissue. There was no stria in the remaining muscle fiber and atrophic fibers of different level were shown. Some muscle fibers showed some degree of necrosis, muscle nuclear membranes increasing. Some myofibers showed internally located nuclei and hyperplastic connective tissue. But there were no neurogenic features. Pyramidal cell from cerebral frontal lobe showed ischemic change and the Purkinje cells from cerebellum were partly exfoliative, chromatin dissolving. Frozen sections from cardiac muscles showed dystrophy and substitution by connective tissue and adipose tissue.ï¼›there were many large blocks of scars in epicardium of left ventricle; some cardiac muscle cells disappeared and some lymphocytes and monocytes infiltrating; cardiac endocardium thickening.Ultrastructure analysis was performed on patient's tissue: nuclear changes were observed in nuclei of skeletal muscles. Different degree of abnormalities in the nuclei, ranging from marked condensation of the chromatin, pyknosis, myofilaments splitting and dissolved to complete damage of the nuclear component, were observed in some of the cells.