A novel lamin A/C mutation in a family with dilated cardiomyopathy, prominent conduction system disease, and need for permanent pacemaker implantation.
BACKGROUND
The LMNA gene, which encodes the nuclear envelope protein lamin A/C, is thought to be the most common of 8 autosomal disease genes implicated in familial dilated cardiomyopathy (FDC). Each family reported to date has a unique mutation and variable degrees of cardiac conduction system, dilated cardiomyopathy, or skeletal muscle disease.


RESULTS
Coding regions of the LMNA gene were screened in 12 biological members of a family with dilated cardiomyopathy and conduction system disease. A novel missense mutation (Leu215Pro) in exon 4 was identified in 8 subjects. Disease was manifested as brady- and tachyarrhythmias, often necessitating permanent pacemaker implantation, and later onset of dilated cardiomyopathy and heart failure. No features of skeletal muscle disease were noted. The high percentage of affected individuals who needed pacemaker therapy (88%) was a unique characteristic of this family compared with other FDC families with LMNA mutations.


CONCLUSIONS
Careful examination of clinical data in families with FDC and LMNA mutations may reveal subtle genotype-phenotype correlations. Knowledge of such correlations may help to further define the mechanisms of disease in LMNA-associated FDC and can assist in the monitoring of disease for at-risk family members.
Hershberger
Ray E
RE
Department of Medicine, Oregon Health and Science University, Portland, Ore 97201, USA. hershber@ohsu.edu
Hanson
Emily L
EL
Jakobs
Petra M
PM
Keegan
Hugh
H
Coates
Kelly
K
Bousman
Sylvia
S
Litt
Michael
M
D000328:Adult; D001145:Arrhythmias, Cardiac / Q000150:complications* / Q000235:genetics* / Q000601:surgery; D002311:Cardiomyopathy, Dilated / Q000150:complications* / Q000235:genetics* / Q000601:surgery; D005260:Female; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010138:Pacemaker, Artificial; D010375:Pedigree; D010641:Phenotype
D034904:Lamin Type A; C440308:lamin C