Aims: The mutations most frequently associated with dilated cardiomyopathy (DCM) have been reported in the lamin A/C gene. The role of variants of the lamin A/C gene was investigated in patients with DCM from eastern and southern Finland. Methods and results: All 12 exons of the lamin A/C gene were screened in 18 well-characterised familial DCM patients from eastern and southern Finland and in 72 sporadic DCM patients from eastern Finland using the PCR-SSCP method. A novel mutation, Ser143Pro (S143P), was detected in the lamin A/C gene in 24 subjects from 5 unrelated families and in one sporadic case of DCM. Sinus or atrioventricular nodal dysfunction occurred in the majority of the affected subjects, many of which required pacemaker implantation. Seven patients (28%) with the S143P mutation died suddenly or from progressive heart failure, or underwent heart transplantation. The haplotypes 5-5-5-3, 5-5-5-2, and 5-5-5-1 co-segregated with the Ser143Pro mutation, suggesting a founder effect of this mutation. Conclusions: A novel mutation S143P in the lamin A/C gene was found to be common among Finnish DCM patients. Haplotype analysis strongly suggests a founder effect of this mutation. The phenotype is characterised by severe heart failure, progressive atrioventricular conduction defects, and sudden death. Screening for the lamin A/C gene and, particularly, the S143P mutation seems warranted when patients with DCM have conduction system disturbances. © 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
Kärkkäinen, S., Heliö, T., Miettinen, R., Tuomainen, P., Peltola, P., Rummukainen, J., … Peuhkurinen, K. (2004). A novel mutation, Ser143Pro, in the lamin A/C gene is common in finnish patients with familial dilated cardiomyopathy. European Heart Journal, 25(10), 885–893. https://doi.org/10.1016/j.ehj.2004.01.020