Missense mutations in desmin associated with familial cardiac and skeletal myopathy.
Desmin-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 cells. The underlying molecular mechanisms are unknown. Involvement of the desmin gene (DES) has been excluded in three families diagnosed with desmin-related myopathy. 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.
Goldfarb
L G
LG
Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892, USA. goldfarb@codon.nih.gov
Park
K Y
KY
Cervenáková
L
L
Gorokhova
S
S
Lee
H S
HS
Vasconcelos
O
O
Nagle
J W
JW
Semino-Mora
C
C
Sivakumar
K
K
Dalakas
M C
MC
D000328:Adult; D017668:Age of Onset; D000368:Aged; D009202:Cardiomyopathies / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003893:Desmin / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*
D003893:Desmin