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 2010, Vol.145 (2), p.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: Report
• Language: English
• ISSN: 1874-1754
• DOI: 10.1016/j.ijcard.2010.04.032

BACKGROUNDThe 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.AIMSTo describe the phenotype associated with the R820W mutation identified in a human family.METHODSThe 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.RESULTSThe 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 homozygous 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.CONCLUSIONThe 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.