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


OBJECTIVE
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 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.


CONCLUSIONS
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.
Ripoll Vera
Tomás
T
Cardiology Department, Hospital Son Llatzer, Palma de Mallorca, Spain. Electronic address: tripoll@hsll.es.
Monserrat Iglesias
Lorenzo
L
Instituto de Investigación Biomédica de A Coruña, Spain.
Hermida Prieto
Manuel
M
Instituto de Investigación Biomédica de A Coruña, Spain.
Ortiz
Martin
M
Instituto de Investigación Biomédica de A Coruña, Spain.
Rodriguez Garcia
Isabel
I
Instituto de Investigación Biomédica de A Coruña, Spain.
Govea Callizo
Nancy
N
Genetics Unit, Hospital Son Dureta, Palma de Mallorca, Spain.
Gómez Navarro
Carlos
C
Cardiology Department, Hospital de Torrecárdenas, Almería, Spain.
Rosell Andreo
Jordi
J
Genetics Unit, Hospital Son Dureta, Palma de Mallorca, Spain.
Gámez Martínez
José María
JM
Cardiology Department, Hospital Son Llatzer, Palma de Mallorca, Spain.
Pons Lladó
Guillermo
G
Cardiology Department, Clínica Palmaplanas, Palma de Mallorca, Spain.
Cremer Luengos
David
D
Cardiology Department, Hospital Son Llatzer, Palma de Mallorca, Spain.
Torres Marqués
Joan
J
Cardiology Department, Hospital Son Llatzer, Palma de Mallorca, Spain.
D000328:Adult; D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002415:Cats; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000235:genetics*; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D000099163:Myosin Binding Protein C