Nature Genetics
3, 333 - 337 (1993)
doi:10.1038/ng0493-333
A disease locus for familial hypertrophic cardiomyopathy maps to chromosome 1q3Hugh Watkins1, 2, Calum MacRae2, 3, Ludwig Thierfelder1, Yah-Huei Chou3, Michael Frenneaux4, William McKenna2, J.G. Seidman3
& Christine E. Seidman1
1Cardiology Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
2Department of Cardiological Sciences, St. George's Hospital Medical School, London SW17 ORE, UK
3Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
4Department of Medicine, Royal Brisbane Hospital, Queensland 4029, Australia Correspondence should be addressed to H.W. Familial hypertrophic cardiomyopathy (FHC) is caused by missense mutations in the  cardiac myosin heavy chain (MHC) gene in less than half of affected individuals. To identify the location of another gene involved in this disorder, a large family with FHC not linked to the MHC gene was studied. Linkage was detected between the disease in this family and a locus on chromosome 1q3 (maximum multipoint lod score = 8.47). Analyses in other families with FHC not linked to the MHC gene, revealed linkage to the chromosome 1 locus in two and excluded linkage in six. Thus mutations in at least three genetic loci can cause FHC. Three sarcomeric contractile proteins — troponin I, tropomyosin and actin — are strong candidate FHC genes at the chromosome 1 locus.
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