Desmin-related myopathy: clinical, electrophysiological, radiological, neuropathological and genetic studies.
Ten Spanish patients from six unrelated families diagnosed with desmin-related myopathy (DRM) were studied. The pattern of DRM inheritance was autosomal dominant in three families, autosomal recessive in one, and there was no family history in two cases. The disease onset was in early adulthood. Cardiac myopathy was the initial presentation in two patients, respiratory insufficiency in one, and lower limb weakness in all others. Cardiac involvement was observed in four patients. Lens opacities were found in four. CK level was normal or slightly elevated, and electrophysiological examination was consistent with myopathy. Muscle biopsies identified intracytoplasmic desmin-immunoreactive inclusions. In addition to desmin, synemin, actin, gelsolin, ubiquitin, alphaB-crystallin and amyloid betaA4 were also present in the deposits. Ultrastructural examination revealed areas of myofibrillary disruption, abnormal electron-dense structures and accumulations of granulofilamentous material. A missense R406W mutation and a novel single amino acid deletion in the desmin gene were identified in two patients; the other patients did not show mutations in desmin, synemin, syncoilin or alphaB-crystallin genes. Analysis of 10 Spanish DRM cases illustrates a wide clinical, myopathological and genetic spectrum of DRM, reinforcing the need for further exploration of genetic causes for this group of disorders.
Olivé
Montse
M
Institut de Neuropatologia, Hospital de Bellvitge, C/Feixa Llarga s/n degrees, 08907 Hospitalet de Llobregat, Barcelona, Spain. 25169mop@comb.es
Goldfarb
Lev
L
Moreno
Dolores
D
Laforet
Encarna
E
Dagvadorj
Ayush
A
Sambuughin
Nyamkhishig
N
Martínez-Matos
Juan Antonio
JA
Martínez
Francesca
F
Alió
Josefina
J
Farrero
Eva
E
Vicart
Patrick
P
Ferrer
Isidro
I
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics; D002386:Cataract / Q000235:genetics; D002648:Child; D003893:Desmin / Q000235:genetics*; D004576:Electromyography; D005260:Female; D006327:Heart Block / Q000235:genetics; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D011494:Protein Kinases / Q000235:genetics; D012131:Respiratory Insufficiency / Q000235:genetics; D014057:Tomography, X-Ray Computed; D038203:alpha-Crystallin B Chain
C059215:CRYAB protein, human; D003893:Desmin; D007381:Intermediate Filament Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C503784:SYNC protein, human; D038203:alpha-Crystallin B Chain; C430456:desmuslin; D011494:Protein Kinases