A molecular basis for familial hypertrophic cardiomyopathy: an alpha/beta cardiac myosin heavy chain hybrid gene.
An alpha/beta cardiac myosin heavy chain (MHC) hybrid gene is coinherited with familial hypertrophic cardiomyopathy (FHC) in one kindred. FHC is a disease of the heart muscle characterized by a thickening of the left ventricular wall with myocyte and myofibrillar disarray that is inherited as an autosomal dominant trait. We demonstrate here and in the accompanying article that the cardiac MHC genes, which encode integral myofibrillar components, are mutated in all affected individuals from two unrelated families with FHC. In one kindred, an unequal crossover event during meiosis may have produced the alpha/beta cardiac MHC hybrid gene that is present in affected individuals. We conclude that mutations in the cardiac MHC genes can cause FHC.
Tanigawa
G
G
Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115.
Jarcho
J A
JA
Kass
S
S
Solomon
S D
SD
Vosberg
H P
HP
Seidman
J G
JG
Seidman
C E
CE
D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005796:Genes; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D015879:Myosin Subfragments / Q000235:genetics*; D010375:Pedigree; D055503:Protein Multimerization; D015183:Restriction Mapping
D046911:Macromolecular Substances; D015879:Myosin Subfragments; D004247:DNA