A novel mutation, Ser143Pro, in the lamin A/C gene is common in finnish patients with familial dilated cardiomyopathy

Abstract

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.

Lamin A/C mutations in dilated cardiomyopathy

“…This study also showed that activation of stress response MEK1/ERK1/2 pathway contributes to increased apoptosis in LMNA R225X/WT dermal fibroblasts after electrical stimulation [42]. Moreover, this apoptotic effect could be attenuated by pharmacological blockade of the MEK1/ERK1/2 pathway.…”

Association of the LMNA gene single nucleotide polymorphism rs4641 with bdilated cardiomyopathy

“…In addition, DCM is associated with abnormal electrophysiology caused by conduction disturbances of the sinoatrial and atrioventricular nodes, among others (Perrot et al, 2009). DCM caused by LMNA gene mutation is characterized by early onset of atrioventricularblock prior to the manifestation of DCM; accordingly, high sudden death rate and malignant arrhythmia are common causes of death (Taylor et al, 2003;Kärkkäinen et al, 2004). Many scholars believe that DCM caused by LMNA gene mutation has a worse prognosis than do other etiologies (Mercuri et al, 2005;Sylvius et al, 2005).…”

“…Arbustini et al (2002) found that K97E, E111X, R190W, and E317K were related to DCM, and their results suggested that approximately 33% of patients with DCM and atrioventricular block carried an LMNA gene mutation. Results of the research of Kärkkäinen et al (2004) showed that the S143P mutation played a marked role in the occurrence of DCM. Hershberger et al (2002) investigated a genealogy with DCM and found that approximately 40% of the members carried the L215P mutation on exon 4, although analysis of LMNA gene mutation function could not completely clarify the mechanism by which this variant led to DCM.…”

“…One study showed that approximately a third of DCM with atrioventricular block was caused by LMNA gene mutations, which indicated that the gene mutations could be considered as an important factor for DCM onset (Song et al, 2007). To date, numerous mutations within the LMNA gene locus have been suggested to lead to DCM (Taylor et al, 2003;Vytopil et al, 2003;Kärkkäinen et al, 2004;Ben Yaou et al, 2005); however, the exact mechanism remains to be elucidated.…”

Clinical utility gene card for: Dilated Cardiomyopathy (CMD)

“…9,10 In certain populations, specific mutations may be overrepresented due to a common founder mutation, for example, the LMNA p.Ser143Pro in 7% of the Finnish idiopathic DCM population or the PLN p.Arg14del in up to 15% of Dutch idiopathic DCM patients. 11,12 Several studies have reported that DCM patients carrying more than one disease-associated mutation have an early onset, severe disease expression and a bad prognosis, which is most likely due to a gene-dosage effect. [13][14][15][16] It is expected that next-generation sequencing techniques will identify an increasing number of patients with such complex genotypes.…”