title: Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene.
abstract: Mutations of the LMNA gene, encoding the nuclear envelope proteins lamins A and C, give rise to Emery-Dreifuss muscular dystrophy and to limb-girdle muscular dystrophy 1B (EDMD and LGMD1B). With one exception, all the reported EDMD and LGMD1B mutations are confined to the first 10 exons of the gene. We report four separate cases, with mutations in the same codon of LMNA exon 11, characterized by remarkable variability of clinical findings, in addition to features not previously reported. One patient had congenital weakness and died in early childhood. In two other patients, severe cardiac problems arose early and, in one of these, cardiac signs preceded by many years the onset of skeletal muscle weakness. The fourth case had a mild and late-onset LGMD1B phenotype. Our cases further expand the clinical spectrum associated with mutations in the LMNA gene and provide new evidence of the role played by the C-terminal domain of lamin A.
authors.affiliation: Dubowitz Neuromuscular Centre, Department of Paediatrics, Hammersmith Hospital, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Mercuri
authors.forename: S C
authors.initials: SC
authors.lastname: Brown
authors.forename: P
authors.initials: P
authors.lastname: Nihoyannopoulos
authors.forename: J
authors.initials: J
authors.lastname: Poulton
authors.forename: M
authors.initials: M
authors.lastname: Kinali
authors.forename: P
authors.initials: P
authors.lastname: Richard
authors.forename: R J
authors.initials: RJ
authors.lastname: Piercy
authors.forename: S
authors.initials: S
authors.lastname: Messina
authors.forename: C
authors.initials: C
authors.lastname: Sewry
authors.forename: M M
authors.initials: MM
authors.lastname: Burke
authors.forename: W
authors.initials: W
authors.lastname: McKenna
authors.forename: G
authors.initials: G
authors.lastname: Bonne
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001120:Arginine / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004568:Electrodiagnosis; D005091:Exons / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D005820:Genetic Testing; D006321:Heart / Q000503:physiopathology; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000473:pathology*; D010641:Phenotype; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: D034904:Lamin Type A; C440308:lamin C; D001120:Arginine