Mapping of X-linked myxomatous valvular dystrophy to chromosome Xq28

Myxoid heart disease is frequently encountered in the general population. It corresponds to an etiologically heterogeneous group of diseases, idiopathic mitral valve prolapse (IMVP) being the most common form. A rarely observed form of myxoid heart disease, X-linked myxomatous valvular dystrophy (XMVD), is inherited in an X-linked fashion and is characterized by multivalvular myxomatous degeneration; however, the histopathological features of the mitral valve do not differ significantly from the severe form of IMVP. In this article, we describe the genetic analysis of a large family in which XMVD is associated with a mild hemophilia A. The coagulation factor Vm gene position in Xq28 provided a starting point for the genetic study, which was conducted by use of polymorphic markers. Two-point linkage analysis confirmed this localization, and a maximum LOD score of 6.57 was found at theta = 0 for two polymorphic microsatellite markers, INT-3 and DXS1008, the first one being intronic to the factor Vm gene. Haplotype analysis of this chromosomal region allowed the definition of an 8-cM minimal interval containing the gene for XMVD, between DXS8011 and Xqter.