A familial hypertrophic cardiomyopathy locus maps to chromosome 15q2.

Abstract

We report that a gene responsible for familial hypertrophic cardiomyopathy (FHC) in a kindred with a mild degree of cardiac hypertrophy maps to chromosome 15q2. The gene encoding cardiac actin, located on chromosome 15q, was analyzed and excluded as a candidate for FHC at this locus. Two additional familes with typical FHC were studied and the disorder in one aiso maps to the chromosome 15q2 locus. The maximum combined multipoint logarithm of odds score in the two linked families is 6.02. Although these two kindreds reside in the same country, we believe that their disorder is caused by independent mutations in the 15q2 locus because of the cinical and genotypic differences between affected individuals. Mutations in at least four loci can cause FHC: chromosomes 14ql ((3 cardiac myosin heavy chain gene), 1q3, and 15q2 and another unidentified locus, suggesting substantial genetic heterogeneity.

Reexamination of chromosomal loci of human muscle actin genes by fluorescencein situ hybridization

“…Our result above is consistent with these. Thierfelder et aL (1993) mapped the familial hypertrophic cardiomyopathy locus to chromosome 15q2 and demonstrated that the cardiac actin gene is not there, with which our result is also in a good agreement.…”

Abnormal contractile properties of muscle fibers expressing beta-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy.

“…The disease is often associated with disabling symptoms (angina, dyspnea, palpitations, and syncope) and is the most common cause of sudden death in otherwise healthy young individuals (2)(3)(4). HCM is genetically heterogeneous (5)(6)(7)(8)(9)(10)(11)(12)(13). The phenotype in HCM may be caused by one of several disease genes (5)(6)(7)(8)(9)(10)(11)(12)(13).…”

“…HCM is genetically heterogeneous (5)(6)(7)(8)(9)(10)(11)(12)(13). The phenotype in HCM may be caused by one of several disease genes (5)(6)(7)(8)(9)(10)(11)(12)(13). In about a third of HCM kindreds, the disease is caused by 1 of at least 30 distinct mutations in the /-myosin heavy chain (f3-MHC) gene located on chromosome 14 (5,6,9,10,(14)(15)(16)(17)(18).…”

A New Locus for Arrhythmogenic Right Ventricular Dysplasia on the Long Arm of Chromosome 14

“…Likewise, genetic heterogeneity has as well as other markers in the same region (corresponding to loci D14S71, D14S76, D14S61, and been found by molecular genetic studies in other myocardial disorders. In familial hypertrophic cardiomyop-D14S74) yield clearly negative lod scores (incidentally, the latter group of markers was also negative even in athy, mutations in chromosomes 1q3 (cardiac troponin T gene) (Watkins et al, 1993;Thierfelder et al, 1994), the study of Rampazzo et al, 1994).…”

“…All polymorphisms were scored without knowlmajor and minor criteria were considered: the diagnosis of ARVD edge of phenotypic data and by two independent observers. Twodepended on the presence of two major criteria from different diagpoint and multipoint lod scores were calculated using the LINKAGE nostic groups, of one major plus two minor criteria, or of four minor software package Version 5.2 (Lathrop et al, 1984; Lathrop and Lacriteria. The clinical status of the affected and unaffected relatives louel, 1985) on a SUN SPARC Server 10-401 computer.…”