Andrew Geddes Engel

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Myofibrillar myopathy (MFM) is a morphologically distinct disorder in which disintegration of the Z-disk and then of the myofibrils is followed by abnormal accumulation of multiple proteins. Mutations in desmin, alphaB-crystallin, and myotilin, all Z-disk-related proteins, cause MFM in the minority of cases. ZASP (a Z-band alternatively spliced PDZ(More)
OBJECTIVE Myofibrillar myopathies (MFMs) are morphologically distinct but genetically heterogeneous muscular dystrophies in which disintegration of Z disks and then of myofibrils is followed by ectopic accumulation of multiple proteins. Cardiomyopathy, neuropathy, and dominant inheritance are frequent associated features. Mutations in alphaB-crystallin,(More)
Choline acetyltransferase (ChAT; EC ) catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses. Mutations in genes encoding ChAT affecting motility exist in Caenorhabditis elegans and Drosophila, but no CHAT mutations have been observed in humans to date. Here we report that mutations in CHAT cause a(More)
Mutations in genes encoding the epsilon, delta, beta and alpha subunits of the end plate acetylcholine (ACh) receptor (AChR) are described and functionally characterized in three slow-channel congenital myasthenic syndrome patients. All three had prolonged end plate currents and AChR channel opening episodes and an end plate myopathy with loss of AChR from(More)
In 76 muscle specimens (normal controls, 9; Duchenne dystrophy, 11; scleroderma, 11; dermatomyositis, 13; polymyositis, 15; inclusion body myositis, 17), mononuclear cells were analyzed at perivascular, perimysial, and endomysial sites of accumulation. Monoclonal antibodies reactive for B cells, T cells, T cell subsets, killer (K) or natural killer (NK)(More)
Inclusion body myositis (IBM) was suspected on light microscopic grounds in 48 of 170 consecutive patients with inflammatory myopathies. One or more vacuoles containing membranous material, groups of atrophic fibres, and an autoaggressive endomysial inflammatory exudate occurred in 100, 96 and 92% of the muscle specimens. All three of these features were(More)
The term myofibrillar myopathy (MFM) was proposed in 1996 as a non-committal term for a pathological pattern of myofibrillar dissolution associated with accumulation of myofibrillar degradation products and ectopic expression of multiple proteins that include desmin, alphaB-crystallin (alphaBC), dystrophin and congophilic amyloid material. Subsequent(More)
In the Lambert-Eaton myasthenic syndrome (LEMS), there is a decreased release of acetylcholine quanta from the nerve terminal by nerve impulse. Recently, an autoimmune origin of LEMS was documented by passive transfer of its electrophysiologic features from man to mouse with IgG. Freeze-fracture electron microscopy of LEMS neuromuscular junctions has(More)