Clinical and myopathological characteristics of desminopathy caused by a mutation in desmin tail domain.
BACKGROUND
Most of the previously described pathogenic mutations in desmin are located in highly conserved α-helical domains that play an important role in intermediate filament assembly. The role of the C-terminus non-α-helical 'tail' domain is much less investigated and until recently mutations in this domain have been implicated in only a few patients. The majority of reported desminopathy cases caused by the tail mutations were sporadic, creating a representation bias regarding the disease frequency and phenotypic characteristics.


METHODS
We performed detailed genotype-phenotype analysis of autosomal dominant desminopathy associated with tail domain mutations in a four-generation autosomal dominant family with 16 members affected by a progressive cardiac and/or skeletal myopathy caused by a c.1346A>C (p.Lys449Thr) mutation located in the tail domain of desmin.


RESULTS
Phenotypic features in patients with tail domain mutations are similar to those in patients with mutations localized in the 1B and 2B α-helical domains.


CONCLUSIONS
We recommend that the tail domain is searched for mutations as intensely as desmin coil domains which until recently were considered to be more 'functional'.
Department of Neurology, Nottingham University Hospitals, Queens Medical Centre, Nottingham, UK. paul.maddisson@nhs.net
Paul
P
Maddison
Maxwell S
MS
Damian
Caroline
C
Sewry
Catherine
C
McGorrian
John B
JB
Winer
Zagaa
Z
Odgerel
Alexey
A
Shatunov
Hee Suk
HS
Lee
Lev G
LG
Goldfarb
D000328:Adult; D000368:Aged; D003893:Desmin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007382:Intermediate Filaments / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D010375:Pedigree
D003893:Desmin