Hypertrophic cardiomyopathy: two homozygous cases with "typical" hypertrophic cardiomyopathy and three new mutations in cases with progression to dilated cardiomyopathy.
About 10% of cases of hypertrophic cardiomyopathy (HCM) evolve into dilated cardiomyopathy (DCM) with unknown causes. We studied 11 unrelated patients (pts) with HCM who progressed to DCM (group A) and 11 who showed "typical" HCM (group B). Mutational analysis of the beta-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), and cardiac troponin T (TNNT2) genes demonstrated eight mutations affecting MYH7 or MYBPC3 gene, five of which were new mutations. In group A-pts, the first new mutation occurred in the myosin head-rod junction and the second occurred in the light chain-binding site. The third new mutation leads to a MYBPC3 lacking titin and myosin binding sites. In group B, two pts with severe HCM carried two homozygous MYBPC3 mutations and one with moderate hypertrophy was a compound heterozygous for MYBPC3 gene. We identified five unreported mutations, potentially "malignant" defects as for the associated phenotypes, but no specific mutations of HCM/DCM.
Nanni
Luisa
L
CRIBI Biotechnology Center, Università degli Studi di Padova, Padua, Italy.
Pieroni
Maurizio
M
Chimenti
Cristina
C
Simionati
Barbara
B
Zimbello
Rosanna
R
Maseri
Attilio
A
Frustaci
Andrea
A
Lanfranchi
Gerolamo
G
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002311:Cardiomyopathy, Dilated / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D020107:Troponin T / Q000097:blood / Q000235:genetics / Q000378:metabolism; D024723:Ventricular Myosins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D009124:Muscle Proteins; D020107:Troponin T; D024723:Ventricular Myosins; D000099163:Myosin Binding Protein C