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Desmin-related myopathy (OMIM #601419) Desmin-related myopathy (DRM) was the first non-keratin intermediate filament disorder identified, and is associated with recessive or dominant mutations in the desmin type III intermediate filament gene, DES. DRM describes a subtype of myofibrillar myopathy characterised by accumulations of desmin protein: the myofibrillar myopathies are chronic neuromuscular disorders accompanied by structural disintegration of the muscle Z-line and accumulations of protein in the muscle fibres. Clinical features include progressive weakness in skeletal muscles, cardiac arrhythmia and other irregularities of heart function. Desmin-related myopathy disorders can also be caused by mutations in B-crystallin. Cases of dominant, recessive and compound heterozygote mutations have been reported. Desminopathies show quite varied degrees of severity, from early to late onset, and may affect cardiac or skeletal muscle preferentially, or both. Studies on mouse models indicate that muscle lacking functional desmin is compromised in its ability to resist physical stress. Associated type III intermediate filament proteins: desmin [Refs]
Dilated cardiomyopathy 1I (CMD1I; OMIM #604765) Idiopathic dilated cardiomyopathy caused by mutations in desmin (DES) is clinically very hard to distinguish from similar disorders caused by mutations in other cardiac cytoskeleton proteins; mutations causing similar phenotypes have also been reported in myosin, actin and troponin T. Associated type III intermediate filament proteins: desmin [Refs]
Alexander disease (OMIM #203450) This progressive neurological degenerative disease is characterized by rapid clinical decline and rapid head growth from onset of the disease, and is usually fatal within the first decade. Infantile Alexander disease produces megencaphaly within the first year of life, which progresses to spasticity and dementia. Patients suffer seizures, somnolence and a range of cognitive and developmental defects. White matter defects can be seen histologically and by MRI as frontal leukoencephaly. Astrocytes are affected and accumulate Rosenthal fibres and features of chronic gliosis. The disease is caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP), a type III intermediate filament protein. Associated type III intermediate filament proteins: glial fibrillary acidic protein [Refs]
Amyotrophic lateral sclerosis 1 (ALS1; OMIM #105400) This disorder has been associated with the type III neuronal intermediate filament gene peripherin, PRPH, as well as with mutations in the NF-H neurofilament gene (see below). (Note: This PRPH gene peripherin is not to be confused with another gene named peripherin, the RDS gene expressed in the retina, nor with PRPH2 which is mutated in pigmentosa. Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by loss of motor neurons in the brain, brainstem and spinal cord, leading to fatal paralysis; it usually begins with asymmetric involvement of the muscles during adult life. ALS is also referred to as 'Lou Gehrig disease' after the famous American baseball player who was diagnosed with the disorder. Associated type III intermediate filament proteins: peripherin Other associated intermediate filament proteins: NF-H, NF-L, NF-M [Refs]
Desmin-related limb-girdle muscular dystrophy This disorder is characterized by proximal muscle weakness and wasting, accompanied frequently with pronounced cardiac involvement. Proximal leg weakness may lead to paresis. Marked atrophy and fatty degeneration of proximal and distal leg muscles is often predominant in the dorsal leg compartment. Associated type III intermediate filament proteins: desmin [Refs] Distal myopathy This is an adult-onset disorder with gait disturbance due to distal leg weakness. Other extremities may involve bulbar, respiratory and facial muscles. Cardiac involvement in the form of arrhythmias, conduction blocks and congestive failure may result in premature demise. It differs from other phenotypically similar disorders in its rapidity of progression, fatal course and pathologic features.
Associated type III intermediate filament proteins: desmin [Refs] Scapuloperoneal syndrome type Kaeser (OMIM #181400) This is an adult-onset, autosomal dominant disorder with an unusual distribution of weakness and wasting involving the proximal musculature in the upper limbs and the distal muscles in the lower limbs. Facial weakness, dysphagia and gynaecomastia are frequent additional symptoms.
Associated type III intermediate filament proteins: desmin [Refs] Dilated cardiomyopathy 1A (CMD1A; OMIM #115200) Dilated cardiomyopathy is a heart muscle disease characterized by ventricular dilatation and reduced systolic function. It represents an outcome of a heterogeneous group of inherited and acquired disorders. It is resulting in high mortality due to sudden death or heart failure. The mode of the disease manifestation is age-dependent without peripheral muscle involvement. Associated type III intermediate filament proteins: desmin Other associated intermediate filament proteins: lamin A, lamin C1 [Refs] Dilated cardiomyopathy with conduction system defects (DCM-CD) This disorder is characterized by conduction system defects including sinus bradycardia, atrioventricular conduction block, or atrial arrhythmias. This group of disorders is highly heterogeneous with numerous loci and 21 different genes linked to DCM to date. LMNA mutations have been associated with autosomal dominant DCM-CD. Associated type III intermediate filament proteins: desmin Other associated intermediate filament proteins: lamin A [Refs] Familial restrictive cardiomyopathy 2 (RCM2; OMIM %609578) Associated type III intermediate filament proteins: desmin [Refs] Last modified: August 27 2008 16:55:00. |
