Evidence of genetic locus heterogeneity for familial bicuspid aortic valve.

Objective We sought to determine if the gene responsible for bicuspid aortic valve (BAV) in an extended family corresponds to previously reported loci for inherited forms of the disorder. Background Loci at 15q25.1-26 and 9q34 have been reported to be associated with cardiovascular abnormalities involving BAV. Methods Linkage analysis was performed on DNA collected from a large multigenerational family in which BAV disease segregates in an autosomal dominant manner, using microsatellite markers from the regions previously reported to segregate with the phenotype. Results Lod scores were determined for genetic markers near the NOTCH1 gene and for a locus on chromosome 15q25.1-26 previously reported as being linked to BAV. The lod scores were negative or less than 1.0 for all markers tested. Conclusions There is no evidence of linkage of BAV in our pedigree to either the NOTCH1 gene or to the chromosome 15 locus. The disorder in this family appears to be caused by a gene at a novel locus.