Utility of genetic screening in hypertrophic cardiomyopathy: prevalence and significance of novel and double (homozygous and heterozygous) beta-myosin mutations.
Genetic screening of the beta-myosin heavy chain gene (MYH7) was evaluated in 100 consecutive unrelated patients with hypertrophic cardiomyopathy (HCM) and 200 normal unrelated subjects. Seventeen beta-myosin mutations were identified in 19 patients. Notably, 13, or 76%, were novel. Mutations were detected in both alleles in two patients: homozygous for Lys207Gln in one, and heterozygous for Pro211 Leu and Arg663His in another. No mutation was detected in the controls. MYH7-associated HCM was associated with more marked left atrial enlargement and syncope than non-MYH7-related HCM. Our findings indicate that: (1) screening methods should allow identification of novel mutations; and (2) more than one sarcomeric mutation may be present in a patient more commonly than is appreciated. Further studies are necessary to ascertain the clinical consequences of the novel and compound gene abnormalities, and to determine whether correlating functional domain to phenotype provides more useful information about the clinical significance of the molecular defects.
Mohiddin
Saidi A
SA
Inherited Heart Diseases Section, Cardiology Branch, and Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1650, USA.
Begley
David A
DA
McLam
Elisha
E
Cardoso
John-Paul
JP
Winkler
Judith B
JB
Sellers
James R
JR
Fananapazir
Lameh
L
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D015995:Prevalence; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D024723:Ventricular Myosins / Q000235:genetics*
D024723:Ventricular Myosins