Phenotype and prognostic correlations of the converter region mutations affecting the β myosin heavy chain.
OBJECTIVE
The prognostic value of genetic studies in cardiomyopathies is still controversial. Our objective was to evaluate the outcome of patients with cardiomyopathy with mutations in the converter domain of β myosin heavy chain (MYH7).


METHODS
Clinical characteristics and survival of 117 affected members with mutations in the converter domain of MYH7 were compared with 409 patients described in the literature with mutations in the same region.


RESULTS
Twenty-five mutations were evaluated (9 in our families including 3 novel (Ile730Asn, Asp717Gly and Arg719Pro)). Clinical diagnoses were hypertrophic (n=407), dilated (n=15), non-compaction (n=4) and restrictive (n=5) cardiomyopathies, unspecified cardiomyopathy (n=11), sudden death (n=50) and 35 healthy carriers. One hundred eighty-four had events (cardiovascular death or transplant). Median event-free survival was 50±2 years in our patients and 53±3 years in the literature (p=0.27). There were significant differences in the outcome between mutation: Ile736Thr had fewer events than other mutations in the region (p=0.01), while Arg719Gln (p<0.01) had reduced event-free survival.


CONCLUSIONS
Mutations in the converter region are generally associated with adverse prognosis although there are differences between mutations. The identification of a mutation in this particular region provides important prognostic information that should be considered in the clinical management of affected patients.
Health in Code, A Coruña, Spain.
Diego
D
García-Giustiniani
Leviev Heart Center, Sheba Medical Centre, and Tel Aviv University, Tel Aviv, Israel.
Michael
M
Arad
Health in Code, A Coruña, Spain.
Martín
M
Ortíz-Genga
Inherited Cardiovascular Disease Unit, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas Universidade da Coruña (UDC), A Coruña, Spain Red de Investigación Cardiovascular (RIC); RD12/0042/0069, A Coruña, Spain.
Roberto
R
Barriales-Villa
Red de Investigación Cardiovascular (RIC); RD12/0042/0069, A Coruña, Spain.
Xusto
X
Fernández
Inherited Cardiovascular Disease Unit, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas Universidade da Coruña (UDC), A Coruña, Spain.
Isabel
I
Rodríguez-García
Health in Code, A Coruña, Spain.
Andrea
A
Mazzanti
Health in Code, A Coruña, Spain.
Elena
E
Veira
Health in Code, A Coruña, Spain.
Emilia
E
Maneiro
Health in Code, A Coruña, Spain.
Paula
P
Rebolo
Health in Code, A Coruña, Spain.
Iván
I
Lesende
Red de Investigación Cardiovascular (RIC); RD12/0042/0069, A Coruña, Spain.
Laura
L
Cazón
Leviev Heart Center, Sheba Medical Centre, and Tel Aviv University, Tel Aviv, Israel.
Dov
D
Freimark
Cardiac Department, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
Juan Ramón
JR
Gimeno-Blanes
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Christine
C
Seidman
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Jonathan
J
Seidman
The Heart Hospital, London, UK.
William
W
McKenna
Health in Code, A Coruña, Spain Inherited Cardiovascular Disease Unit, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas Universidade da Coruña (UDC), A Coruña, Spain.
Lorenzo
L
Monserrat
D024722:Cardiac Myosins / Q000235:genetics*; D009202:Cardiomyopathies / Q000145:classification / Q000175:diagnosis / Q000235:genetics; D004452:Echocardiography / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D013030:Spain; D016019:Survival Analysis
C501641:MYH7 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains