title: Prevalent cardiac phenotype resulting in heart transplantation in a novel LMNA gene duplication.
abstract: Mutations in the lamin A/C gene (LMNA) are known to be involved in several diseases such as Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy type 1B and dilated cardiomyopathies with conduction disease, with considerable phenotype heterogeneity. Here we report on a novel autosomal dominant mutation in LMNA in two direct relatives presenting with different clinical phenotypes, characterized by severe life-threatening limb-girdle muscle involvement and cardiac dysfunction treated with heart transplantation in the proband, and by ventricular tachyarrhythmias with preserved cardiac and skeletal muscle function in her young son. To our knowledge, this is the first report of a duplication in the LMNA gene. The two phenotypes described could reflect different clinical stages of the same disease. We hypothesize that early recognition and initiation of therapeutic manoeuvres in the younger patient may retard the rate of progression of the cardiomyopathy.
authors.affiliation: Department of Neuroscience, University of Pisa, Via Roma 67, 56126 Pisa, Italy. leda.vol@virgilio.it
authors.forename: L
authors.initials: L
authors.lastname: Volpi
authors.forename: G
authors.initials: G
authors.lastname: Ricci
authors.forename: C
authors.initials: C
authors.lastname: Passino
authors.forename: E
authors.initials: E
authors.lastname: Di Pierri
authors.forename: G
authors.initials: G
authors.lastname: Alì
authors.forename: M
authors.initials: M
authors.lastname: Maccherini
authors.forename: S
authors.initials: S
authors.lastname: Benedetti
authors.forename: G
authors.initials: G
authors.lastname: Lattanzi
authors.forename: M
authors.initials: M
authors.lastname: Columbaro
authors.forename: M
authors.initials: M
authors.lastname: Ferrari
authors.forename: D
authors.initials: D
authors.lastname: Caramella
authors.forename: P
authors.initials: P
authors.lastname: Tanganelli
authors.forename: M
authors.initials: M
authors.lastname: Emdin
authors.forename: G
authors.initials: G
authors.lastname: Siciliano
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D004562:Electrocardiography; D005260:Female; D020440:Gene Duplication; D006321:Heart / Q000503:physiopathology*; D006331:Heart Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D034904:Lamin Type A / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D018908:Muscle Weakness / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D013318:Stroke Volume / Q000502:physiology; D014057:Tomography, X-Ray Computed
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D008565:Membrane Proteins; D009687:Nuclear Proteins; C092710:emerin