title: LMNA mutations in cardiac transplant recipients.
abstract: Lamin A and C are components of the nuclear envelope, located at the nucleoplasmatic surface of the inner nuclear membrane within cells. Recently, mutations within LMNA encoding lamin A/C have been associated with various disease entities including cardiomyopathy. We screened heart transplant recipients suffering from dilated cardiomyopathy (DCM) with a positive family history of LMNA mutations. Four index patients and one relative belonging to four unrelated families carrying LMNA mutations were identified. The mutations p.Q355X and p.S22L have not been reported before, whereas p.R190W has already been reported in other studied DCM cohorts. In the patients of the present study, the mean age at manifestation of heart disease was 37.6 years (range 30-45 years), with progression to end-stage heart failure requiring transplantation at a mean age of 45.8 years (range 35-54 years). Three patients presented initially with atrial fibrillation. These data confirm the involvement of LMNA mutations in patients with DCM and extend the mutational spectrum of LMNA. The p.R190W mutation has been reported in different populations and may therefore be useful for analyzing the impact of a specific LMNA mutation on the phenotype of muscle disease.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pethig
authors.forename: Janine
authors.initials: J
authors.lastname: Genschel
authors.forename: Tina
authors.initials: T
authors.lastname: Peters
authors.forename: Mathias
authors.initials: M
authors.lastname: Wilhelmi
authors.forename: Peer
authors.initials: P
authors.lastname: Flemming
authors.forename: Herbert
authors.initials: H
authors.lastname: Lochs
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Hartmut H-J
authors.initials: HH
authors.lastname: Schmidt
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000601:surgery; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D016027:Heart Transplantation; D006801:Humans; D034904:Lamin Type A; D034882:Lamins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D034882:Lamins