Clinical and myopathological characteristics of desminopathy caused by a mutation in desmin tail domain.

Abstract:

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. CONCLUSION: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'.

journal_name

Eur Neurol

journal_title

European neurology

authors

Maddison P,Damian MS,Sewry C,McGorrian C,Winer JB,Odgerel Z,Shatunov A,Lee HS,Goldfarb LG

doi

10.1159/000341617

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

279-86

issue

5

eissn

0014-3022

issn

1421-9913

pii

000341617

journal_volume

68

pub_type

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