Systematic analysis of the regulatory and essential myosin light chain genes: genetic variants and mutations in hypertrophic cardiomyopathy

Item Type:	Article
Title:	Systematic analysis of the regulatory and essential myosin light chain genes: genetic variants and mutations in hypertrophic cardiomyopathy
Creators Name:	Kabaeva, Z.T. and Perrot, A. and Wolter, B. and Dietz, R. and Cardim, N. and Correia, J.M. and Schulte, H.D. and Aldashev, A.A. and Mirrakhimov, M.M. and Osterziel, K.J.
Abstract:	Hypertrophic cardiomyopathy (HCM) can be caused by mutations in genes encoding for the ventricular myosin essential and regulatory light chains. In contrast to other HCM disease genes, only a few studies describing disease-associated mutations in the myosin light chain genes have been published. Therefore, we aimed to conduct a systematic screening for mutations in the ventricular myosin light chain genes in a group of clinically well-characterised HCM patients. Further, we assessed whether the detected mutations are associated with malignant or benign phenotype in the respective families. We analysed 186 unrelated individuals with HCM for the human ventricular myosin regulatory (MYL2) and essential light chain genes (MYL3) using polymerase chain reaction, single strand conformation polymorphism analysis and automated sequencing. We found eight single nucleotide polymorphisms in exonic and adjacent intronic regions of MYL2 and MYL3. Two MYL2 missense mutations were identified in two Caucasian families while no mutation was found in MYL3. The mutation Glu22Lys was associated with moderate septal hypertrophy, a late onset of clinical manifestation, and benign disease course and prognosis. The mutation Arg58Gln showed also moderate septal hypertrophy, but, in contrast, it was associated with an early onset of clinical manifestation and premature sudden cardiac death. In conclusion, myosin light chain mutations are a very rare cause of HCM responsible for about 1% of cases. Mutations in MYL2 could be associated with both benign and malignant HCM phenotype.
Keywords:	Cardiomyopathy, Myosin Light Chains, Hypertrophy, Sudden Cardiac Death, Genetics
Source:	European Journal of Human Genetics
ISSN:	1018-4813
Publisher:	Nature Publishing Group
Volume:	10
Number:	11
Page Range:	741-748
Date:	November 2002
Official Publication:	https://doi.org/10.1038/sj.ejhg.5200872
PubMed:	View item in PubMed

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