The R820W mutation in the MYBPC3 gene, associated with hypertrophic cardiomyopathy in cats, causes hypertrophic cardiomyopathy and left ventricular non-compaction in humans

• Published in: International journal of cardiology Vol. 145; no. 2; pp. 405 - 407
• Main Authors: Ripoll Vera, Tomás, Monserrat Iglesias, Lorenzo, Hermida Prieto, Manuel, Ortiz, Martin, Rodriguez Garcia, Isabel, Govea Callizo, Nancy, Gómez Navarro, Carlos, Rosell Andreo, Jordi, Gámez Martínez, José María, Pons Lladó, Guillermo, Cremer Luengos, David, Torres Marqués, Joan
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 19-11-2010; Elsevier
• Subjects: Adult; Age; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Cardiology. Vascular system; Cardiomyopathy; Cardiomyopathy, Hypertrophic - diagnosis; Cardiomyopathy, Hypertrophic - genetics; Cardiovascular; Carrier Proteins - genetics; Cats; Emergency and intensive care: neonates and children. Prematurity. Sudden death; Female; Fibrillation; Genetics; Heart; Heart diseases; Humans; Hypertrophy; Intensive care medicine; Male; Medical sciences; Mutation; Mutation - genetics; Myocarditis. Cardiomyopathies; Non-compaction; Pedigree; Sudden death; Ventricle; Ventricular Dysfunction, Left - diagnosis; Ventricular Dysfunction, Left - genetics; Genetics; Cardiomyopathy; Non-compaction; Sudden death; Hypertrophy; Human; Fissipedia; Carnivora; Cardiocirculatory arrest; Cardiovascular disease; Myocardial disease; Left ventricle; Vertebrata; Mammalia; Gene; Cat; Hypertrophic cardiomyopathy; Mutation; Ventricular non compaction; Congenital cardiopathy; Cardiology
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2010.04.032

Abstract Background The R820W mutation in the MYBPC3 gene has been associated with the development of hypertrophic cardiomyopathy (HCM) in rag-doll cats, but had not been described in humans. Aims To describe the phenotype associated with the R820W mutation identified in a human family. Methods The R820W was identified by direct sequencing of the MYBPC3 gene in a 47 year old woman with HCM and left ventricular non-compaction (LVNC). Clinical and genetic studies of the R820W mutation were performed in her family. Results The index patient was homozygous for the mutation and had no additional mutations in the main sarcomeric genes (MYH7, TNNT2, TNNI3, and TPM1). She had HCM with LVNC and normal systolic function. One brother had died suddenly at age 43 years. Another brother diagnosed of LVNC with severe systolic dysfunction and a cardiac arrest was also homozgous for the mutation. One heterozygous 31 year old sister, and three heterozygous sons of the index (ages 14, 20 and 23 years old) were clinically unaffected. The father of the index was apparently healthy and her mother had atrial fibrillation and an electrocardiographic diagnosis of left ventricular hypertrophy at age 86 years. Conclusion The R820W mutation in the MYBPC3 gene, previously associated with HCM in rag-doll cats, causes both HCM and LVNC in homozygous human carriers, with mild or null clinical expression in heterozygous carriers.