[Beta-myosin heavy-chain gene mutations in patients with hypertrophic cardiomyopathy].
OBJECTIVE
To determine the frequency of mutations in the beta-myosin heavy-chain gene (MYH7) in a cohort of patients with hypertrophic cardiomyopathy (HCM) and their families, and to investigate correlations between genotype and phenotype.


METHODS
Single-strand conformation polymorphism analysis and sequencing of fragments with abnormal MYH7 gene mobility were carried out in 128 consecutive index patients with HCM. The phenotypes of patients with and without mutations were compared and the phenotypes of identified families were recorded.


RESULTS
A total of 11 mutations were found in 13 families (10%); 7/11 had been previously described. The I736T mutation was found in three families and the A797T in two. One patient had two mutations (i.e., I736T and R787H). Mutations were more frequent in patients with a family history of sudden death (31%) and in those with severe hypertrophy (39% had a thickness > or = 30 mm). Mutations were found in 29 of 42 members of the 13 families, including six family members (20%) who were healthy carriers and aged < or = 36 years. Sudden death had occurred in eight members of four families: four in two families with the I736T mutation, one in a family with A797T, one in a family with R870H, and two in a family with A901P.


CONCLUSIONS
MYH7 mutations were present in 10% of our families. Mutations were more frequent in patients with a family history of sudden death and in those with severe hypertrophy. Most mutations had been described previously. Some appeared in several families. For some mutations, the correlation between genotype and phenotype was stable, while for others, there were marked differences between the phenotypes of the index patients and their relatives, suggesting the presence of additional genetic factors that have yet to be identified.
Laredo
Rafael
R
Servicio de Cardiología, Complejo Hospitalario Universitario Juan Canalejo e Instituto Universitario de Ciencias de la Salud de la Universidad de A Coruña, A Coruña, Spain.
Monserrat
Lorenzo
L
Hermida-Prieto
Manuel
M
Fernández
Xusto
X
Rodríguez
Isabel
I
Cazón
Laura
L
Alvariño
Inés
I
Dumont
Carlos
C
Piñón
Pablo
P
Peteiro
Jesús
J
Bouzas
Beatriz
B
Castro-Beiras
Alfonso
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D024722:Cardiac Myosins / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D003627:Data Interpretation, Statistical; D016757:Death, Sudden, Cardiac / Q000209:etiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational
C501641:MYH7 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains