Lamin A/C mutations associated with familial and sporadic cases of dilated cardiomyopathy in Koreans

• DOI: 10.1038/emm.2007.13
• Publication Date: 2013-01-17T11:55:03Z
• Authors: Kyuyoung Song; Marie-Pierre Dube; Jiyoung Lim; Ilsun Hwang; Inchul Lee; Jae-Joong Kim
• Keywords: Adult; Cardiomyopathy, Dilated; Male; 0301 basic medicine; Korea; Base Sequence; Molecular Sequence Data; Lamins; Pedigree; 3. Good health; 03 medical and health sciences; Mutation; Humans; Female; Genetic Predisposition to Disease; Amino Acid Sequence

Dilated cardiomyopathy (DCM) is characterized by cardiac dilation and systolic dysfunction. So far sixteen genes have been shown to cause autosomal dominant familial dilated cardiomyopathy (FDC). We identified a large Korean family from the Jeju island showing a clear Mendelian inheritance of FDC. A genomewide linkage scan at 9 cM marker density identified a peak multipoint LOD score of 2.82 at D1S195. Haplotyping of the region with 15 additional markers defined a candidate interval that included a known candidate gene encoding the lamin A/C (LMNA). Sequencing of the LMNA exons revealed one missense mutation at C568T (Arg190Trp) in the alpha-helical rod domain of the LMNA gene co-segregating with FDC with conduction-system disease. The same mutation was found in patients of another Korean family with FDC without conduction-system disease. Upon screening 14 sporadic DCM cases, we found three LMNA mutations including a case having a previously described (Glu161Lys) mutation and two having novel mutations (Glu53Val and Glu186Lys). Our results suggest that variable genotypes of laminopathy are implicated in not only familial but also considerable proportion of sporadic DCM.