Natural history of dilated cardiomyopathy due to lamin A/C gene mutations

Matthew R.G. Taylor, Pamela R. Fain, Gianfranco Sinagra, Misi L. Robinson, Alastair D. Robertson, Elisa Carniel, Andrea Di Lenarda, Teresa J. Bohlmeyer, Debra A. Ferguson, Gary L. Brodsky, Mark M. Boucek, Jean Lascor, Andrew C. Moss, Wai Lun P. Li, Gary L. Stetler, Francesco Muntoni, Michael R. Bristow, Luisa Mestroni, Dmi Dao, Sharon L. GrawLisa Ku, Brian D. Lowes, Xiao Zhu, Katherine Gowan, William M. Old, Mauro Driussi, Giulio Scherl

Research output: Contribution to journalArticle

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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. METHODS: 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.

Original languageEnglish (US)
Pages (from-to)771-780
Number of pages10
JournalJournal of the American College of Cardiology
Volume41
Issue number5
DOIs
StatePublished - Mar 5 2003

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Taylor, M. R. G., Fain, P. R., Sinagra, G., Robinson, M. L., Robertson, A. D., Carniel, E., Di Lenarda, A., Bohlmeyer, T. J., Ferguson, D. A., Brodsky, G. L., Boucek, M. M., Lascor, J., Moss, A. C., Li, W. L. P., Stetler, G. L., Muntoni, F., Bristow, M. R., Mestroni, L., Dao, D., ... Scherl, G. (2003). Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. Journal of the American College of Cardiology, 41(5), 771-780. https://doi.org/10.1016/S0735-1097(02)02954-6