Mapping of X-Linked Myxomatous Valvular Dystrophy to Chromosome Xq28

Abstract

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 VIII 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 straight theta=0 for two polymorphic microsatellite markers, INT-3 and DXS1008, the first one being intronic to the factor VIII 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.

Periostin Induces Intracellular Cross-talk between Kinases and Hyaluronan in Atrioventricular Valvulogenesis

“…We have found similarity both in the expression patterns of PN and FLNA and in the phenotypes of PN and FLNA knock-out mice, each of which have inhibited ECM remodeling of primordial AV valve (10,53). This phenotype is also characteristically seen in patients with mitral valve prolapse, including a nonsyndromic subset of patients with point mutations in FLNA (52,54,55). Filamin A is an ACTIN-binding protein that anchors various transmembrane proteins to the cytoskeleton, and it provides a scaffold for many cytoplasmic signaling proteins involved in ACTIN cytoskeleton remodeling.…”

“…The process begins at midgestation (about E14.5) when PN expression begins to increase, and it finishes postnatally as PN expression declines to a low, barely detectable baseline level (51,52). This suggested a potential role for PN in valvulogenesis that was confirmed by globally deleting the PN gene (10,65).…”

“…Studies have identified point mutations in FLNA in patients with nonsyndromic, myxomatous valvular diseases like mitral valve prolapse (51,52). We have found similarity both in the expression patterns of PN and FLNA and in the phenotypes of PN and FLNA knock-out mice, each of which have inhibited ECM remodeling of AV valve primordia (10,(52)(53)(54)(55). FLNA is an ACTIN-binding protein that anchors various transmembrane proteins to the cytoskeleton, and it provides a scaffold for many cytoplasmic signaling proteins involved in ACTIN cytoskeleton remodeling.…”

“…We have focused on ␤1-INTEGRIN for contractile function of cushion cells because this specific INTEGRIN also regulates the ACTIN-binding protein, filamin-A (FLNA) (50). Studies have identified point mutations in FLNA in patients with nonsyndromic, myxomatous valvular diseases like mitral valve prolapse (51,52). We have found similarity both in the expression patterns of PN and FLNA and in the phenotypes of PN and FLNA knock-out mice, each of which have inhibited ECM remodeling of AV valve primordia (10,(52)(53)(54)(55).…”

Lack of Association Between Perlecan Gene Intron 6 BamHI Polymorphism and Risk of Mitral Valve Prolapse in Taiwan Chinese

“…18) In addition, Xlinked inheritance has been reported in a special form of familial MVP, called myxomatous valvular dystrophy, which has been mapped to Xq28 in a large French pedigree. 19) Low blood pressure and autonomic dysfunction may be regarded as a phenotypic feature of MVP. 20,21) The renin-angiotensin system was hypothesized to be involved in the pathogenesis of mitral valve prolapse syndrome (MVPS).…”