Nature Genetics
19, 402 - 403 (1998)
doi:10.1038/1300
Missense mutations in desmin associated with familial cardiac and skeletal
myopathyLev G. Goldfarb1, Kye-Yoon Park1, Larisa Cervenáková2, 3, Svetlana Gorokhova1, 2, Hee-Suk Lee1, Olavo Vasconcelos1, James W. Nagle1, Christina Semino-Mora1, Kumaraswamy Sivakumar1, 4
& Marinos C. Dalakas11
Medical Neurology Branch, Bethesda, Maryland 20892, USA. 2
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892, USA. 3
American Red Cross J.H. Holland Laboratory, Rockville, Maryland 20855, USA. 4
Barrow Neurological Institute, Phoenix, Arizona 85013, USA.
Correspondence should be addressed to Lev G. Goldfarb goldfarb@codon.nih.govDesmin-related myopathy (OMIM 601419) is a familial disorder characterized
by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias
and restrictive heart failure, and by intracytoplasmic accumulation of desmin-reactive
deposits in cardiac and skeletal muscle cells1,
2,
3,
4. The
underlying molecular mechanisms are unknown. Involvement of the desmin gene
(DES) has been excluded in three families diagnosed with desmin-related
myopathy5. We report two new families with desmin-related cardioskeletal
myopathy associated with mutations in the highly conserved carboxy-terminal
end of the desmin rod domain. A heterozygous A337P mutation was identified
in a family with an adult-onset skeletal myopathy and mild cardiac involvement.
Compound heterozygosity for two other mutations, A360P and N393I, was detected
in a second family characterized by childhood-onset aggressive course of cardiac
and skeletal myopathy.
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