| Title | Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. | | Author(s) | Taylor MR, Fain PR, Sinagra G, Robinson ML, Robertson AD, Carniel E, Di Lenarda A, Bohlmeyer TJ, Ferguson DA, Brodsky GL, Boucek MM, Lascor J, Moss AC, Li WL, Stetler GL, Muntoni F, Bristow MR, Mestroni L, Familial Dilated Cardiomyopathy Registry Research Group | | Institution | University of Colorado Cardiovascular Institute, Denver, Colorado 80010, USA. | | Source | J Am Coll Cardiol 2003 Mar 5; 41(5):771-80. | | MeSH | Amino Acid Sequence
Cardiomyopathy, Dilated
Child, Preschool
Chromatography, High Pressure Liquid
Cohort Studies
DNA Mutational Analysis
Female
Follow-Up Studies
Genetic Predisposition to Disease
Genotype
Humans
Male
Mutation, Missense
Nuclear Lamina
Pedigree
Phenotype
Polymerase Chain Reaction
Prevalence
Probability
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Risk Assessment
Severity of Illness Index
Statistics, Nonparametric
Survival Rate
| | Abstract | OBJECTIVES: We examined the prevalence, genotype-phenotype correlation, and natural history of lamin A/C gene (LMNA) mutations in subjects with dilated cardiomyopathy (DCM).
BACKGROUND: Mutations in LMNA have been found in patients with DCM with familial conduction defects and muscular dystrophy, but the clinical spectrum, prognosis, and clinical relevance of laminopathies in DCM are unknown.
BACKGROUND: A cohort of 49 nuclear families, 40 with familial DCM and 9 with sporadic DCM (269 subjects, 105 affected), was screened for mutations in LMNA using denaturing high-performance liquid chromatography and sequence analysis. Bivariate analysis of clinical predictors of LMNA mutation carrier status and Kaplan-Meier survival analysis were performed.
RESULTS: Mutations in LMNA were detected in four families (8%), three with familial (R89L, 959delT, R377H) and one with sporadic DCM (S573L). There was significant phenotypic variability, but the presence of skeletal muscle involvement (p < 0.001), supraventricular arrhythmia (p = 0.003), conduction defects (p = 0.01), and "mildly" DCM (p = 0.006) were predictors of LMNA mutations. The LMNA mutation carriers had a significantly poorer cumulative survival compared with non-carrier DCM patients: event-free survival at the age of 45 years was 31% versus 75% in non-carriers.
CONCLUSIONS: Mutations in LMNA cause a severe and progressive DCM in a relevant proportion of patients. Mutation screening should be considered in patients with DCM, in particular when clinical predictors of LMNA mutation are present, regardless of family history. | | Language | eng | | Pub Type(s) | Journal Article
Multicenter Study
| | PubMed ID | 12628721 |
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