title: Lamin A/C mutations associated with familial and sporadic cases of dilated cardiomyopathy in Koreans.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea. kysong@amc.seoul.kr
authors.forename: Kyuyoung
authors.initials: K
authors.lastname: Song
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Dubé
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Lim
authors.forename: Ilsun
authors.initials: I
authors.lastname: Hwang
authors.forename: Inchul
authors.initials: I
authors.lastname: Lee
authors.forename: Jae-Joong
authors.initials: JJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007723:Korea; D034882:Lamins / Q000145:classification / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree
chemical_list: D034882:Lamins