A Novel Myosin Essential Light Chain Mutation Causes Hypertrophic Cardiomyopathy with Late Onset and Low Expressivity
Hypertrophic cardiomyopathy (HCM) is caused by mutations in genes encoding sarcomere proteins. Mutations in MYL3, encoding the essential light chain of myosin, are rare and have been associated with sudden death. Both recessive and dominant patterns of inheritance have been suggested. We studied a l...
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| Language: | English |
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Wiley
2012-01-01
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| Series: | Biochemistry Research International |
| Online Access: | http://dx.doi.org/10.1155/2012/685108 |
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| author | Paal Skytt Andersen Paula Louise Hedley Stephen P. Page Petros Syrris Johanna Catharina Moolman-Smook William John McKenna Perry Mark Elliott Michael Christiansen |
| author_facet | Paal Skytt Andersen Paula Louise Hedley Stephen P. Page Petros Syrris Johanna Catharina Moolman-Smook William John McKenna Perry Mark Elliott Michael Christiansen |
| author_sort | Paal Skytt Andersen |
| collection | DOAJ |
| description | Hypertrophic cardiomyopathy (HCM) is caused by mutations in genes encoding sarcomere proteins. Mutations in MYL3, encoding the essential light chain of myosin, are rare and have been associated with sudden death. Both recessive and dominant patterns of inheritance have been suggested. We studied a large family with a 38-year-old asymptomatic HCM-affected male referred because of a murmur. The patient had HCM with left ventricular hypertrophy (max WT 21 mm), a resting left ventricular outflow gradient of 36 mm Hg, and left atrial dilation (54 mm). Genotyping revealed heterozygosity for a novel missense mutation, p.V79I, in MYL3. The mutation was not found in 300 controls, and the patient had no mutations in 10 sarcomere genes. Cascade screening revealed a further nine heterozygote mutation carriers, three of whom had ECG and/or echocardiographic abnormalities but did not fulfil diagnostic criteria for HCM. The penetrance, if we consider this borderline HCM the phenotype of the p.V79I mutation, was 40%, but the mean age of the nonpenetrant mutation carriers is 15, while the mean age of the penetrant mutation carriers is 47. The mutation affects a conserved valine replacing it with a larger isoleucine residue in the region of contact between the light chain and the myosin lever arm. In conclusion, MYL3 mutations can present with low expressivity and late onset. |
| format | Article |
| id | doaj-art-a0689cb1788c490abed7c35ccb96892f |
| institution | Kabale University |
| issn | 2090-2247 2090-2255 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Biochemistry Research International |
| spelling | doaj-art-a0689cb1788c490abed7c35ccb96892f2025-02-03T05:59:05ZengWileyBiochemistry Research International2090-22472090-22552012-01-01201210.1155/2012/685108685108A Novel Myosin Essential Light Chain Mutation Causes Hypertrophic Cardiomyopathy with Late Onset and Low ExpressivityPaal Skytt Andersen0Paula Louise Hedley1Stephen P. Page2Petros Syrris3Johanna Catharina Moolman-Smook4William John McKenna5Perry Mark Elliott6Michael Christiansen7Department of Clinical Biochemistry and Immunology, Statens Serum Institut, 2300S Copenhagen, DenmarkDepartment of Clinical Biochemistry and Immunology, Statens Serum Institut, 2300S Copenhagen, DenmarkThe Heart Hospital, University College London Hospital, London, UKThe Heart Hospital, University College London Hospital, London, UKDepartment of Biomedical Sciences, University of Stellenbosch, Cape Town, South AfricaThe Heart Hospital, University College London Hospital, London, UKThe Heart Hospital, University College London Hospital, London, UKDepartment of Clinical Biochemistry and Immunology, Statens Serum Institut, 2300S Copenhagen, DenmarkHypertrophic cardiomyopathy (HCM) is caused by mutations in genes encoding sarcomere proteins. Mutations in MYL3, encoding the essential light chain of myosin, are rare and have been associated with sudden death. Both recessive and dominant patterns of inheritance have been suggested. We studied a large family with a 38-year-old asymptomatic HCM-affected male referred because of a murmur. The patient had HCM with left ventricular hypertrophy (max WT 21 mm), a resting left ventricular outflow gradient of 36 mm Hg, and left atrial dilation (54 mm). Genotyping revealed heterozygosity for a novel missense mutation, p.V79I, in MYL3. The mutation was not found in 300 controls, and the patient had no mutations in 10 sarcomere genes. Cascade screening revealed a further nine heterozygote mutation carriers, three of whom had ECG and/or echocardiographic abnormalities but did not fulfil diagnostic criteria for HCM. The penetrance, if we consider this borderline HCM the phenotype of the p.V79I mutation, was 40%, but the mean age of the nonpenetrant mutation carriers is 15, while the mean age of the penetrant mutation carriers is 47. The mutation affects a conserved valine replacing it with a larger isoleucine residue in the region of contact between the light chain and the myosin lever arm. In conclusion, MYL3 mutations can present with low expressivity and late onset.http://dx.doi.org/10.1155/2012/685108 |
| spellingShingle | Paal Skytt Andersen Paula Louise Hedley Stephen P. Page Petros Syrris Johanna Catharina Moolman-Smook William John McKenna Perry Mark Elliott Michael Christiansen A Novel Myosin Essential Light Chain Mutation Causes Hypertrophic Cardiomyopathy with Late Onset and Low Expressivity Biochemistry Research International |
| title | A Novel Myosin Essential Light Chain Mutation Causes Hypertrophic Cardiomyopathy with Late Onset and Low Expressivity |
| title_full | A Novel Myosin Essential Light Chain Mutation Causes Hypertrophic Cardiomyopathy with Late Onset and Low Expressivity |
| title_fullStr | A Novel Myosin Essential Light Chain Mutation Causes Hypertrophic Cardiomyopathy with Late Onset and Low Expressivity |
| title_full_unstemmed | A Novel Myosin Essential Light Chain Mutation Causes Hypertrophic Cardiomyopathy with Late Onset and Low Expressivity |
| title_short | A Novel Myosin Essential Light Chain Mutation Causes Hypertrophic Cardiomyopathy with Late Onset and Low Expressivity |
| title_sort | novel myosin essential light chain mutation causes hypertrophic cardiomyopathy with late onset and low expressivity |
| url | http://dx.doi.org/10.1155/2012/685108 |
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